Aging involves morphological and functional changes across different organs, but how these changes are linked among the different organs remains to be elucidated. Here, we uncover a central role of platelets in systemic aging. In aged mice, the levels of platelet-secreted pro-inflammatory factors (PSPF) increased greatly in the serum and platelets, leading to a diffuse increase of platelet infiltration in the brain, liver, lung, kidney, and aortic root. The RNA-binding protein HuR/ELAVL1, a major regulator of RNA metabolism, promoted the production of PSPF in platelets. Platelet-specific deletion of HuR reduced the expression of PSPF in platelets, alleviated platelet infiltration in the brain, liver, lung, kidney, and aortic root, and delayed systemic aging. By using single-nucleus sequencing, platelet-specific HuR ablation was found to alleviate p53 and pro-inflammatory signaling pathways in liver, lung, and brain tissues in aged mice. Our findings highlight a role of platelets in coordinating aging traits across organs.

BACKGROUND:Vulnerable plaque rupture is a major mechanism underlying acute coronary events, but imaging-based risk assessment using individual plaque features remains limited. The histology-derived vulnerability index (VI) integrates multiple plaque components and is associated with adverse cardiovascular outcomes but requires ex vivo assessment. Optical coherence tomography (OCT) enables high-resolution in vivo plaque characterization, and the OCT-derived index of plaque attenuation (IPA) may provide a quantitative measure of integrated plaque vulnerability. AIMS:This study aimed to determine the association between OCT-derived IPA and histological VI and to identify the histological plaque components contributing to IPA. METHODS:In 240 coronary blocks from 10 human cadaveric hearts, co-registered OCT and histology were performed. IPA was calculated from attenuation images. Histology quantified necrotic core, collagen, α-SMA+ area, and macrophages (CD68+, CD206+). Associations were assessed using correlation and multivariable regression. RESULTS:IPA at a 9 mm-1 threshold (IPA9) correlated with VI (r = 0.714, p < 0.001) and discriminated high-VI blocks (AUC = 0.852). CD68+ macrophage area (β = 17.20, p < 0.001) and necrotic core (β = 1.39, p = 0.013) predicted higher IPA, whereas collagen and α-SMA+ area were inversely associated. CD206+ areas were not independently related with IPA, but the CD206+/CD68+ ratio significantly improved IPA model performance (ΔR2 = 0.023, p = 0.004). CONCLUSIONS:OCT-derived IPA closely corresponds to histological VI and is primarily driven by necrotic core and pro-inflammatory macrophage infiltration. IPA may serve as a clinically obtainable quantitative OCT marker for integrated assessment of inflammation-weighted plaque vulnerability.

INTRODUCTION:The objective of the study was to evaluate the capability of magnetocardiography (MCG) in distinguishing obstructive coronary heart disease (OCHD) from coronary microvascular dysfunction (CMVD). METHODS:Patients with chest pain suspected of having CAD were consecutively enrolled in according to the inclusion and exclusion criteria. All patients underwent coronary angiography and coronary blood flow analysis, and were divided into OCHD group (n = 447) and CMVD group (n = 332) based on the results of imaging analysis. All patients also underwent MCG examination before or after coronary angiology in 48 h, the MCG parameters were analyzed by an independent third party. Univariate and multivariate logistic regression analyses were performed to identify significant clinical and MCG parameters between groups. Diagnostic models were constructed using selected MCG parameters alone or in combination with clinical indicators. Performance was assessed using receiver operating characteristic curves, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Clinical utility and model performance were further validated via calibration curves and decision curve analysis. RESULTS:In OCHD group, the prevalence of type 2 diabetes mellitus (35.79% vs. 25.30%, p = 0.022) and interventricular septal thickness (mm) (11.00 [10.25-12.00] vs. 11.00 [10.00-11.00], p < 0.001) was significantly higher than those in the CMVD group, while high-density lipoprotein cholesterol (mmol/L) was significantly lower (1.01 [0.85-1.16] vs. 1.06 [0.93-1.22], p < 0.001). Seven MCG parameters showed significant intergroup differences: QR-enav (10.08 [9.02-11.22] vs. 9.36 [8.38-10.41], p < 0.001), RS-enav (10.29 [9.32-11.33] vs. 9.66 [8.71-10.73], p < 0.001), TT-dicar (0.04 [0.02-0.14] vs. 0.02 [0.01-0.09], p < 0.001), TT-dicd (41.40 [25.75-77.55] vs. 34.40 [20.83-62.90], p < 0.001), TT-didav (60.70 [55.50-66.40] vs. 63.80 [58.02-67.80], p < 0.001), TT-didmse (3.70 [2.10-6.35] vs. 2.90 [1.70-4.77], p < 0.001), and TT-enav (10.44 [9.20-11.57] vs. 9.96 [8.79-11.01], p < 0.001). RS-enav achieved the highest AUC (0.615), with sensitivity, specificity, PPV, and NPV of 48.77%, 69.21%, 70.10%, and 47.72%, respectively. TT-didmse exhibited specificity of 73.51% and PPV of 69.41%, while TT-enav showed specificity of 60.26% and PPV of 67.21%. TT-dicd demonstrated the highest diagnostic sensitivity (78.30%) in distinguishing OCHD patients from CMVD. The integrated model combining seven MCG parameters yielded an AUC of 0.681 (95% CI: 0.642-0.720), which improved to 0.713 (95% CI: 0.674-0.751) in the combined model. Calibration curves confirmed high agreement between nomogram predictions and observed outcomes, and decision curve analysis indicated better net benefit for the combined model. CONCLUSION:MCG parameters, either alone or in combination with clinical indicators, demonstrate feasibility in distinguishing OCHD from CMVD. As a novel noninvasive diagnostic tool, MCG holds potential value in discriminating between OCHD and CMVD.

Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3' UTR of Dgat2 mRNA and intron 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3' UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.

BACKGROUND FAVOR III China (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) reported improved clinical outcomes in quantitative flow ratio (QFR) relative to angiography-guided percutaneous coronary intervention (PCI), but the clinical impact of QFR-guided PCI according to sex remains unknown. OBJECTIVES The authors sought to compare sex differences in the 2-year clinical benefits of a QFR-guided PCI strategy and to evaluate the differences in outcomes between men and women undergoing contemporary PCI. METHODS This study involved a prespecified subgroup analysis of the FAVOR III China trial, in which women and men were randomized to a QFR-guided strategy or a standard angiography-guided strategy. Sex differences in clinical benefit of the QFR guidance were analyzed for major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization within 2 years. RESULTS A total of 1,126 women and 2,699 men were eligible and the occurrence of 2-year MACE was similar between women and men (10.3% vs 10.5%; P = 0.96). Compared with an angiography-guided strategy, a QFR-guided strategy resulted in a 7.9% and 9.7% reduction in PCI rates in men and women, respectively. A QFR-guided strategy resulted in similar relative risk reductions for 2-year MACE in women (8.0% vs 12.7%; HR: 0.62; 95% CI: 0.42-0.90) and men (8.7% vs 12.4%; HR: 0.69; 95% CI: 0.54-0.87) (Pinteraction = 0.61). Furthermore, QFR values were not significantly different between men and women with various angiographic stenosis categories. CONCLUSIONS A QFR-guided PCI strategy resulted in improved MACE in both men and women at 2 years compared with an angiography-guided PCI strategy. The FAVOR III China Study [FAVOR III China]; (NCT03656848) (JACC: Asia 2024;4:201-212) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

OBJECTIVE To evaluate the role of resting magnetocardiography in identifying severe coronary artery stenosis in patients with suspected coronary artery disease. METHODS A total of 513 patients with angina symptoms were included and divided into two groups based on the extent of coronary artery disease determined by angiography: the non-severe coronary stenosis group (< 70% stenosis) and the severe coronary stenosis group (≥ 70% stenosis). The diagnostic model was constructed using magnetic field map (MFM) parameters, either individually or in combination with clinical indicators. The performance of the models was evaluated using receiver operating characteristic curves, accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Calibration plots and decision curve analysis were performed to investigate the clinical utility and performance of the models, respectively. RESULTS In the severe coronary stenosis group, QR_MCTDd, S_MDp, and TT_MAC50 were significantly higher than those in the non-severe coronary stenosis group (10.46 ± 10.66 vs. 5.11 ± 6.07, P < 0.001; 7.2 ± 8.64 vs. 4.68 ± 6.95, P = 0.003; 0.32 ± 57.29 vs. 0.26 ± 57.29, P < 0.001). While, QR_MVamp, R_MA, and T_MA in the severe coronary stenosis group were lower (0.23 ± 0.16 vs. 0.28 ± 0.16, P < 0.001; 55.06 ± 48.68 vs. 59.24 ± 53.01, P < 0.001; 51.67 ± 39.32 vs. 60.45 ± 51.33, P < 0.001). Seven MFM parameters were integrated into the model, resulting in an area under the curve of 0.810 (95% CI: 0.765–0.855). The sensitivity, specificity, PPV, NPV, and accuracy were 71.7%, 80.4%, 93.3%, 42.8%, and 73.5%; respectively. The combined model exhibited an area under the curve of 0.845 (95% CI: 0.798–0.892). The sensitivity, specificity, PPV, NPV, and accuracy were 84.3%, 73.8%, 92.6%, 54.6%, and 82.1%; respectively. Calibration curves demonstrated excellent agreement between the nomogram prediction and actual observation. The decision curve analysis showed that the combined model provided greater net benefit compared to the magnetocardiography model. CONCLUSIONS The novel quantitative MFM parameters, whether used individually or in combination with clinical indicators, have been shown to effectively predict the risk of severe coronary stenosis in patients presenting with angina-like symptoms. Magnetocardiography, an emerging non-invasive diagnostic tool, warrants further exploration for its potential in diagnosing coronary heart disease.

Fluid flow transport through the trabecular meshwork tissues is a major regulator of intraocular pressure (IOP) modulation in healthy and glaucomatous individuals. Microbead occlusion models of ocular hypertension regulate aqueous humor drainage to induce high IOP to allow for in vivo study of pressure-related glaucomatous pathology. However, the reliability and application of current injectable microbeads are hindered by inadequate design of the beads-tissue interfaces to maintain a stable IOP elevation over the long term. Considering the graded, porous architecture and fluid transport of the trabecular meshwork, we developed a tailored, injectable "viscobeads" technique, which induced a sustained elevation of IOP for at least 8 weeks. These composite viscobeads contain a non-degradable polystyrene (PS) core for structural support and a biodegradable polylactic-co-glycolic acid (PLGA) viscoelastic surface. This approach enhances the obstruction of aqueous humor drainage through heterogeneous sizes of trabecular meshwork fenestrations and reliably modulates the magnitude and duration of ocular hypertension. In a mouse model, a single viscobeads injection resulted in sustained IOP elevation (average 21.4±1.39 mm Hg), leading to a 34% retinal ganglion cell (RGC) loss by 56 days. In an earlier stage of glaucoma progression, we conducted non-invasive electroretinography (ERG) recording and revealed glaucomatous progression by analyzing high-frequency oscillatory potentials. To further explore the application of the viscobeads glaucoma models, we assayed a series of genes through adeno-associated virus (AAV)-mediated screening in mice and assessed the impact of genetic manipulation on RGC survivals. CRISPR mediated disruption of the genes, PTEN, ATF3 and CHOP enhanced RGC survival while LIN 28 disruption negatively impacted RGC survival. This biologically driven viscobeads design provides an accessible approach to investigate chronic intraocular hypertension and glaucoma-like neurodegeneration and ultimately tenders the opportunity to evaluate genetic and pharmacological therapeutics.

OBJECTIVE:To assess the safety and effectiveness of intravascular lithotripsy (IVL) treatment for de novo coronary lesion involving severely calcified vessels in a Chinese population.METHODS:The Clinical Trial of the ShOckwave Coronary IVL System Used to Treat CalcIfied Coronary ArtEries (SOLSTICE) was a prospective, single-arm, multicentre trial. According to the inclusion criteria, patients with severely calcified lesions were enrolled in the study. IVL was used to perform calcium modification prior to stent implantation. The primary safety endpoint was freedom from major adverse cardiac events (MACEs) at 30 days. The primary effectiveness endpoint was procedural success, defined as successful stent delivery with residual stenosis < 50% by core lab assessment without in-hospital MACEs. The morphological changes of calcium modification were assessed by optical coherence tomography (OCT) before and after IVL treatment.RESULTS:Patients (n = 20) were enrolled at three sites in China. Severe calcification by core lab assessment was present in all lesions, with a mean calcium angle and thickness of 300 ± 51° and 0.99 ± 0.12 mm (by OCT), respectively. The 30-day MACE rate was 5%. Both primary safety and effectiveness endpoints were achieved in 95% of patients. The final in-stent diameter stenosis was 13.1% ± 5.7% with no patient had a residual stenosis < 50% after stenting. No serious angiographic complications (severe dissection grade D or worse, perforation, abrupt closure, slow flow/no-reflow) observed at any time during the procedure. OCT imaging demonstrated visible multiplane calcium fracture in 80% of lesions with a mean stent expansion of 95.62% ± 13.33% at the site of maximum calcification and minimum stent area (MSA) of 5.34 ± 1.64 mm2.CONCLUSIONS:The initial coronary IVL experience for Chinese operators resulted in high procedural success and low angiographic complications consistent with prior IVL studies, reflecting the relative ease of use of IVL technology.

Rational Excessive mitochondrial fission is considered key process involved in myocardial ischemia/reperfusion (I/R) injury. However, the upstream mechanism remains largely unclear. Decreased level of Kruppel Like Factor 4 (KLF4) has been implicated in the pathogenesis of mitochondrial dysfunction and heart's adaption to stress. However, the role of Klf4 in I/R process is not fully elucidated. This study aims to investigate how Klf4 regulates mitochondrial dynamics and further clarify its underlying mechanism during cardiac I/R injury. Methods Loss-of-function and gain-of-function strategies were applied to investigate the role of Klf4 in cardiac I/R injury via genetic ablation or intra-myocardial adenovirus injection. Mitochondrial dynamics was analyzed by confocal microscopy in vitro and transmission electron microscopy in vivo. Chromatin immunoprecipitation and luciferase reporter assay were performed to explore the underlying mechanisms. Results KLF4 was downregulated in I/R heart. Cardiac-specific Klf4 knockout significantly exacerbated cardiac dysfunction in I/R mice. Mechanistically, Klf4 deficiency aggravated mitochondrial apoptosis, reduced ATP generation and boosted ROS overproduction via enhancing DRP1-dependent mitochondrial fission. ROCK1 was identified as a kinase regulating DRP1 activity at Ser616. Klf4 deficiency upregulated the expression of ROCK1 at transcriptional level, thus increasing S616-DRP1-mediated mitochondrial fission during I/R. Finally, reconstitution of Klf4 inhibited mitochondrial fission, restored mitochondrial function and alleviated I/R injury. Conclusion Our study provides the first evidence that Klf4 deficiency exacerbates myocardial I/R injury through regulating ROCK1 expression at transcriptional level to induce DRP1-mediated mitochondrial fission. Targeting mitochondrial dynamics by restoring Klf4 might be potentially cardio-protective strategies attenuating I/R injury.

Atherosclerosis preferentially develops at bifurcations exposed to disturbed flow. Plexin D1 (PLXND1) responds to mechanical forces and drives macrophage accumulation in atherosclerosis. Here, multiple strategies were used to identify the role of PLXND1 in site-specific atherosclerosis. Using computational fluid dynamics and three-dimensional light-sheet fluorescence-microscopy, the elevated PLXND1 in M1 macrophages was mainly distributed in disturbed flow area of ApoE-/ -carotid bifurcation lesions, and visualization of atherosclerosis in vivo was achieved by targeting PLXND1. Subsequently, to simulate the microenvironment of bifurcation lesions in vitro, we co -cultured oxidized low-density lipoprotein (oxLDL)-treated THP-1-derived macrophages with shear-treated human umbilical vein endothelial cells (HUVECs). We found that oscillatory shear induced the increase of PLXND1 in M1 macrophages, and knocking down PLXND1 inhibited M1 polarization. Semaphorin 3E, the ligand of PLXND1 which was highly expressed in plaques, strongly enhanced M1 macrophage polarization via PLXND1 in vitro. Our findings provide in-sights into pathogenesis in site-specific atherosclerosis that PLXND1 mediates disturbed flow -induced M1 macrophage polarization.

BACKGROUND:This head-to-head, multicenter, randomized trial investigated the safety and efficacy of Restore (Cardionovum, Bonn, Germany) drug-coated balloon (DCB) angioplasty in an Asian patient population with coronary drug-eluting stent in-stent restenosis (DES-ISR). METHODS:A total of 240 patients with coronary DES-ISR were treated with Restore DCB or with SeQuent® Please (Braun, Melsungen, Germany) DCB. This trial used nine-month in-segment late lumen loss (LL) as the primary endpoint. Secondary endpoints included two-year clinical event rates. RESULTS:Patient, lesion, and procedural characteristics in both treatment groups were similar. Nine-month in-segment LL was 0.38 ± 0.50 mm with Restore vs. 0.35 ± 0.47 mm with SeQuent® Please (p for non-inferiority = 0.02). The two-year follow-up rates were 95.8 % (115/120) in the Restore group and 94.2 % (113/120) in the SeQuent® Please group. Both groups had similar one- and two-year target lesion failure (TLF) rates (13.3 % vs. 12.6 %; p = 0.87 at one year, 14.8 % vs. 15.0 %; p = 1.0 at two years). Moreover, the all-cause mortality and myocardial infarction rates were 0 and 3.5 % (4/120) in the Restore group and 0.9 % (1/120) and 3.5 % (4/120) in the SeQuent® Please group, respectively. Additional analyzing of vessel quantitative flow ratio (QFR) did also show noninferior outcomes for one explicit treatment bunch. CONCLUSIONS:The two-year follow-up indicated sustained long-term clinical safety and efficacy for both devices on the basis of QFR value.

Stem cell-based therapy has been used to treat ischaemic heart diseases for two decades. However, optimal cell types and transplantation methods remain unclear. This study evaluated the therapeutic effects of human umbilical cord mesenchymal stem cell (hUCMSC) sheet on myocardial infarction (MI). Methods: hUCMSCs expressing luciferase were generated by lentiviral transduction for in vivo bio-luminescent imaging tracking of cells. We applied a temperature-responsive cell culture surface-based method to form the hUCMSC sheet. Cell retention was evaluated using an in vivo bio-luminescent imaging tracking system. Unbiased transcriptional profiling of infarcted hearts and further immunohistochemical assessment of monocyte and macrophage subtypes were used to determine the mechanisms underlying the therapeutic effects of the hUCMSC sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, angiogenesis and left ventricular remodelling. Results: When transplanted to the infarcted mouse hearts, hUCMSC sheet significantly improved the retention and survival compared with cell suspension. At the early stage of MI, hUCMSC sheet modulated inflammation by decreasing Mcp1-positive monocytes and CD68-positive macrophages and increasing Cx3cr1-positive non-classical macrophages, preserving the cardiomyocytes from acute injury. Moreover, the extracellular matrix produced by hUCMSC sheet then served as bioactive scaffold for the host cells to graft and generate new epicardial tissue, providing mechanical support and routes for revascularsation. These effects of hUCMSC sheet treatment significantly improved the cardiac function at days 7 and 28 post-MI. Conclusions: hUCMSC sheet formation dramatically improved the biological functions of hUCMSCs, mitigating adverse post-MI remodelling by modulating the inflammatory response and providing bioactive scaffold upon transplantation into the heart. Translational perspective: Due to its excellent availability as well as superior local cellular retention and survival, allogenic transplantation of hUCMSC sheets can more effectively acquire the biological functions of hUCMSCs, such as modulating inflammation and enhancing angiogenesis. Moreover, the hUCMSC sheet method allows the transfer of an intact extracellular matrix without introducing exogenous or synthetic biomaterial, further improving its clinical applicability.

BACKGROUND Healed plaques are frequently found in patients with acute coronary syndrome, but the prognostic value is debatable. This study investigated the clinical features of non-culprit healed plaques detected by optical coherence tomography（OCT） with the aim of predicting plaque progression of healed plaques.METHODS This study retrospectively analyzed 113 non-culprit lesions from 85 patients who underwent baseline OCT imaging and follow-up angiography from January 2015 to December 2019. Plaque progression predictors were assessed by multivariate analysis.RESULTS Among 113 non-culprit lesions, 27 healed plaques（23.9%） were identified. Patients with non-culprit healed plaques had prior antiplatelet therapy（65.0% vs. 33.8%, P = 0.019）, hypertension（85.0% vs. 50.7%, P = 0.009）, and dyslipidemia（70.0% vs.41.5%, P = 0.04） which were more frequently than those without healed plaques. The thickness（r = 0.674, P ＜ 0.001）, arc（r = 0.736,P ＜ 0.001）, and volume（r = 0.541, P = 0.004） of healed plaque were correlated with minimum lumen diameter changes. At a mean follow-up of 11.5 months, the non-culprit healed plaques had a lower minimum lumen diameter（1.61 ± 0.46 mm vs. 1.91 ± 0.73 mm,P = 0.016）, lower average lumen diameter（1.86 mm vs. 2.10 mm, P = 0.033）, and a higher degree of diameter stenosis（41.4% ±11.9% vs. 35.5% ± 13.1%, P = 0.031） when compared to baseline measurements. The plaque progression rate was higher in the healed plaque group（33.3% vs. 8.1%, P = 0.002）, and multivariate analysis identified healed plaques [odds ratio（OR） = 8.49, 95% CI:1.71-42.13] and lumen thrombus（OR = 10.69, 95% CI: 2.21-51.71） as predictors of subsequent lesion progression.CONCLUSIONS Healed plaques were a predictor for rapid plaque progression. The quantitative parameters of healed plaque showed a good agreement with plaque progression. Patients with healed plaque were associated with prior antiplatelet therapy and high level of low-density lipoprotein cholesterol. Bifurcation lesions might be the predilection sites of healed plaques.

Our previous research has shown that type-2a Sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA2a) undergoes posttranscriptional oxidative modifications in cardiac microvascular endothelial cells (CMECs) in the context of excessive cardiac oxidative injury. However, whether SERCA2a inactivity induces cytosolic Ca 2+ imbalance in mitochondrial homeostasis is far from clear. Mitofusin2 (Mfn2) is well known as an important protein involved in endoplasmic reticulum (ER)/mitochondrial Ca 2+ tethering and the regulation of mitochondrial quality. Therefore, the aim of our study was to elucidate the specific mechanism of SERCA2a-mediated Ca 2+ overload in the mitochondria via Mfn2 tethering and the survival rate of the heart under conditions of cardiac microvascular ischemic injury. In vitro , CMECs extracted from mice were subjected to 6 h of hypoxic injury to mimic ischemic heart injury. C57-WT and Mfn2 KO mice were subjected to a 1 h ischemia procedure via ligation of the left anterior descending branch to establish an in vivo cardiac ischemic injury model. TTC staining, immunohistochemistry and echocardiography were used to assess the myocardial infarct size, microvascular damage, and heart function. In vitro , ischemic injury induced irreversible oxidative modification of SERCA2a, including sulfonylation at cysteine 674 and nitration at tyrosine 294/295, and inactivation of SERCA2a, which initiated calcium overload. In addition, ischemic injury-triggered [Ca 2+ ]c overload and subsequent [Ca 2+ ]m overload led to mPTP opening and ΔΨm dissipation compared with the control. Furthermore, ablation of Mfn2 alleviated SERCA2a-induced mitochondrial calcium overload and subsequent mito-apoptosis in the context of CMEC hypoxic injury. In vivo , compared with that in wild-type mice, the myocardial infarct size in Mfn2 KO mice was significantly decreased. In addition, the findings revealed that Mfn2 KO mice had better heart contractile function, decreased myocardial infarction indicators, and improved mitochondrial morphology. Taken together, the results of our study suggested that SERCA2a-dependent [Ca 2+ ]c overload led to mitochondrial dysfunction and activation of Mfn2-mediated [Ca 2+ ]m overload. Overexpression of SERCA2a or ablation of Mfn2 expression mitigated mitochondrial morphological and functional damage by modifying the SERCA2a/Ca 2+ -Mfn2 pathway. Overall, these pathways are promising therapeutic targets for acute cardiac microvascular ischemic injury.

BACKGROUND:Evaluating prospectively the feasibility, accuracy and reproducibility of optical flow ratio (OFR), a novel method of computational physiology based on optical coherence tomography (OCT). METHODS AND RESULTS:Sixty consecutive patients (76 vessels) underwent prospectively OCT, angiography- based quantitative flow ratio (QFR) and fractional flow ratio (FFR). OFR was computed offline in a central core-lab by analysts blinded to FFR. OFR was feasible in 98.7% of the lesions and showed excellent agreement with FFR (ICCa = 0.83, r = 0.83, slope = 0.80, intercept = 0.17, kappa = 0.84). The area under curve to predict an FFR ≤ 0.80 was 0.95, higher than for QFR (0.91, p = 0.115) and for minimal lumen area (0.64, p < 0.001). Diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 93%, 92%, 93%, 88%, 96%, 13.8, 0.1, respectively. Median time to obtain OFR was 1.07 (IQR: 0.98-1.16) min, with excellent intraobserver and interobserver reproducibility (0.97 and 0.95, respectively). Pullback speed had negligible impact on OFR, provided the same coronary segment were imaged (ICCa = 0.90, kappa = 0.697). CONCLUSIONS:The prospective computation of OFR is feasible and reproducible in a real-world series, resulting in excellent agreement with FFR, superior to other image-based methods.

The relationship between normal thyroid function and type 2 diabetes mellitus (T2DM) has been a particular focus for concern. The present study determined the relationship between thyroid hormone levels and the prevalence of diabetic retinopathy (DR) in T2DM patients. A cross-sectional study (n = 633) was performed in Xi'an, Shaanxi Province, China. Subjects were evaluated for anthropometric measurements, thyroid function, and diabetic retinopathy. Logistic regression models were used to assess the relationships between thyroid hormones and DR. Of 633 patients, 243 (38.4%) patients suffered from DR. The prevalence of DR showed a significantly decreasing trend across the quartiles based on free triiodothyronine (FT3) (FT3 quartile 1 group [FT3-Q1] <4.35 pmol/L, FT3 quartile 2 group [FT3-Q2] 4.35-4.70 pmol/L, FT3 quartile 3 group [FT3-Q3] 4.70-5.08 pmol/L, and FT3 quartile 4 group [FT3-Q4] ≥5.08 pmol/L) (56.7%, 42.5%, 33.1%, 23.8%, P < 0.001). In comparison with all participants categorized in FT3-Q1, the multivariable adjusted odds ratios (95% confidence interval) of DR in FT3-Q2, FT3-Q3, and FT3-Q4 were 0.587 (0.340-1.012), 0.458 (0.258-0.813), and 0.368 (0.201-0.673), (P = 0.055, P = 0.008, P = 0.001), respectively. FT3 levels within the normal range are negatively associated with DR in euthyroid patients with type 2 diabetes. Further studies should be aimed at clarifying the relationship between thyroid hormones and T2DM.

Background and aims: Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for ASCVD, the aim of this study was to investigate the effects of a dipeptidyl peptidase-4 inhibitor, sitagliptin, on prevention of progression of coronary atherosclerosis assessed by three-dimensional quantitative coronary angiography (3D-QCA) in T2DM patients with coronary artery disease (CAD). Methods: This was a prospective, randomized, double-center, open-label, blinded end point, controlled 18-month study in patients with CAD and T2DM. A total of 149 patients, who had at least 1 atherosclerotic plaque with 20%-80% luminal narrowing in a coronary artery, and had not undergone intervention during a clinically indicated coronary angiography or percutaneous coronary intervention, were randomized to sitagliptin group (n = 74) or control group (n = 75). Atherosclerosis progression was measured by repeat 3D-QCA examination in 88 patients at study completion. The primary outcome was changes in percent atheroma volume (PAV) from baseline to study completion measured by 3D-QCA. Secondary outcomes included change in 3D-QCA-derived total atheroma volume (TAV) and late lumen loss (LLL). Results: The primary outcome of PAV increased of 1.69% (95%CL, - 0.8%-4.2%) with sitagliptin and 5.12% (95%CL, 3.49%-6.74%) with the conventional treatment (p = 0.023). The secondary outcome of change in TAV in patients treated with sitagliptin increased of 6.45 mm(3) (95%CL,-2.46 to 6.36 mm(3)) and 9.45 mm(3) (95%CL,-4.52 to 10.14 mm(3)) with conventional treatment (p = 0.023), however, no significant difference between groups was observed (p = 0.175). Patients treated with sitagliptin had similar LLL as compared with conventional antidiabetics (- 0.06, 95%CL, - 0.22 to 0.03 vs. - 0.08, - 0.23 to - 0.03 mm, p = 0.689). Conclusions: In patients with type 2 diabetes and coronary artery disease, treatment with sitagliptin resulted in a significantly lower rate of progression of coronary atherosclerosis compared with conventional treatment.

Background Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC). Methods In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC. Results Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose ( P < 0.001), but, poorly on healthy behaviors ( P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes. Conclusion Chinese women’s cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.