Vascular aging is associated with the development of cardiovascular complications, in which endothelial cell senescence (ES) may play a critical role. Nitric oxide (NO) prevents human ES through inhibition of oxidative stress, and inflammatory signaling by mechanisms yet to be elucidated. Endothelial cells undergo an irreversible growth arrest and alter their functional state after a finite number of divisions, a phenomenon called replicative senescence. We assessed the contribution of NO during replicative senescence of human aortic (HAEC) and coronary (CAEC) endothelial cells, in which accumulation of the senescence marker SA-β-Gal was quantified by β-galactosidase staining on cultured cells. We found a negative correlation in passaged cell cultures from P0 to P12, between a reduction in NO production with increased ES and the formation of reactive oxygen (ROS) and nitrogen (ONOO−) species, indicative of oxidative and nitrosative stress. The effect of ES was evidenced by reduced expression of endothelial Nitric Oxide Synthase (eNOS), Interleukin Linked Kinase (ILK), and Heat shock protein 90 (Hsp90), alongside a significant increase in the BH2/BH4 ratio, inducing the uncoupling of eNOS, favoring the production of superoxide and peroxynitrite species, and fostering an inflammatory environment, as confirmed by the levels of Cyclophilin A (CypA) and its receptor Extracellular Matrix Metalloprotease Inducer (EMMPRIN). NO prevents ES by preventing the uncoupling of eNOS, in which oxidation of BH4, which plays a key role in eNOS producing NO, may play a critical role in launching the release of free radical species, triggering an aging-related inflammatory response.

BACKGROUND:Cardiovascular diseases (CVD) impact a substantial portion of the global population and represent a significant threat to experiencing life-threatening outcomes, such as atherosclerosis, myocardial infarction, stroke and heart failure. Despite remarkable progress in pharmacology and medical interventions, CVD persists as a major public health concern, and now ranks as the primary global cause of death and the highest consumer of global budgets. Ongoing research endeavours persist in seeking novel therapeutic avenues and interventions to deepen our understanding of CVD, enhance prevention measures, and refine treatment strategies.METHODS:Nanotechnology applied to the development of new molecular probes with diagnostic and theranostic properties represents one of the greatest technological challenges in preclinical and clinical research.RESULTS:The application of nanotechnology in cardiovascular medicine holds great promise for advancing our understanding of CVDs and revolutionizing their diagnosis and treatment strategies, ultimately improving patient care and outcomes. In addition, the capacity of drug encapsulation in nanoparticles has significantly bolstered their biological safety, bioavailability and solubility. In combination with imaging technologies, molecular imaging has emerged as a pivotal therapeutic tool, offering insight into the molecular events underlying disease and facilitating targeted treatment approaches.CONCLUSION:Here, we present a comprehensive overview of the recent advancements in targeted nanoparticle approaches for diagnosing CVDs, encompassing molecular imaging techniques, underscoring the significant progress in theranostic, as a novel and promising therapeutic strategy.

Background: Endothelial nitric oxide synthase (NOS3) elicits atheroprotection by preventing extracellular matrix (ECM) proteolytic degradation through inhibition of extracellular matrix metalloproteinase inducer (EMMPRIN) and collagenase MMP-13 by still unknown mechanisms. Methods: C57BL/6 mice lacking ApoE, NOS3, and/or MMP13 were fed with a high-fat diet for 6 weeks. Entire aortas were extracted and frozen to analyze protein and nucleic acid expression. Atherosclerotic plaques were detected by ultrasound imaging, Oil Red O (ORO) staining, and Western Blot. RNA-seq and RT-qPCR were performed to evaluate EMMPRIN, MMP-9, and EMMPRIN-targeting miRNAs. Mouse aortic endothelial cells (MAEC) were incubated to assess the role of active MMP-13 over MMP-9. One-way ANOVA or Kruskal-Wallis tests were performed to determine statistical differences. Results: Lack of NOS3 in ApoE null mice fed with a high-fat diet increased severe plaque accumulation, vessel wall widening, and high mortality, along with EMMPRIN-induced expression by upregulation of miRNAs 46a-5p and 486-5p. However, knocking out MMP-13 in ApoE/NOS3-deficient mice was sufficient to prevent mortality (66.6 vs. 26.6%), plaque progression (23.1 vs. 8.8%), and MMP-9 expression, as confirmed in murine aortic endothelial cell (MAEC) cultures, in which MMP-9 was upregulated by incubation with active recombinant MMP-13, suggesting MMP-9 as a new target of MMP-13 in atherosclerosis. Conclusion: We describe a novel mechanism by which the absence of NOS3 may worsen atherosclerosis through EMMPRIN-induced ECM proteolytic degradation by targeting the expression of miRNAs 146a-5p and 485-5p. Focusing on NOS3 regulation of ECM degradation could be a promising approach in the management of atherosclerosis.

Endothelial dysfunction is an early event in coronary microvascular disease. Integrin-linked kinase (ILK) prevents endothelial nitric oxide synthase (eNOS) uncoupling and, thus, endothelial dysfunction. However, the specific role of endothelial ILK in cardiac function remains to be fully elucidated. We hypothesised that endothelial ILK plays a crucial role in maintaining coronary microvascular function and contractile performance in the heart. We generated an endothelial cell-specific ILK conditional knock-out mouse (ecILK cKO) and investigated cardiovascular function. Coronary endothelial ILK deletion significantly impaired cardiac function: ejection fraction, fractional shortening and cardiac output decreased, whilst left ventricle diastolic internal diameter decreased and E/A and E/Eʹ ratios increased, indicating not only systolic but also diastolic dysfunction. The functional data correlated with extensive extracellular matrix remodelling and perivascular fibrosis, indicative of adverse cardiac remodelling. Mice with endothelial ILK deletion suffered early ischaemic-like events with ST elevation and transient increases in cardiac troponins, which correlated with fibrotic remodelling. In addition, ecILK cKO mice exhibited many features of coronary microvascular disease: reduced cardiac perfusion, impaired coronary flow reserve and arterial remodelling with patent epicardial coronary arteries. Moreover, endothelial ILK deletion induced a moderate increase in blood pressure, but the antihypertensive drug Losartan did not affect microvascular remodelling whilst only partially ameliorated fibrotic remodelling. The plasma miRNA profile reveals endothelial-to-mesenchymal transition (endMT) as an upregulated pathway in endothelial ILK conditional KO mice. Our results show that endothelial cells in the microvasculature in endothelial ILK conditional KO mice underwent endMT. Moreover, endothelial cells isolated from these mice and ILK-silenced human microvascular endothelial cells underwent endMT, indicating that decreased endothelial ILK contributes directly to this endothelial phenotype shift. Our results identify ILK as a crucial regulator of microvascular endothelial homeostasis. Endothelial ILK prevents microvascular dysfunction and cardiac remodelling, contributing to the maintenance of the endothelial cell phenotype.

Introduction: Adverse cardiac remodeling following acute myocardial infarction (AMI) depends on how promptly the phagocytic-nuclear system responds. Among strategies to limit the inflammatory response, we have developed a nanoparticle (NIL10) which binds to IL-10 receptor (IL-10R) in-vitro and promotes macrophage polarization towards a resolutive phenotype in animal models of myocardial ischemia-reperfusion (I/R). However, its therapeutic use still depends on understanding its ability to regulate monocyte recruitment. Hypothesis: Targeting the IL-10R in circulating monocytes may represent a new therapeutic approach to improve cardiac function in patients undergoing AMI. Objective: To explore the molecular mechanisms leading to the inhibition of monocyte recruitment by NIL10 in pigs undergoing cardiac I/R. Methods: By using a porcine model of myocardial I/R, we arranged the following groups: (1) control group (2) intravenous administration (IV) 1 mg/kg NIL10, (3) IV of 4x10 5 isolated monocytes from group 2, (4) IV of 4x10 5 isolated monocytes from group 1 and then incubated with NIL10 (A). Results: Groups 2-4 exhibited better cardiac function compared to group 1 (B), which resulted in a decrease in myocardial fibrosis (C), along with a reduction of circulating CCR2+ monocytes (D) and a decrease in classical-monocyte infiltration, as shown by a reduction of CCR2+ macrophages in the necrotic area of the heart (E). As a result, CCL2 plasma expression, a functional ligand of CCR2, was decreased by day 7 post-I/R (F) in contrast to the necrotic tissue expression profile in which we detected large amounts of CCL2 (G) and STAT3 activation, indicative of IL10R activity (H). Conclusion: In addition to macrophage polarization, NIL10 induces cardiac protection by limiting classical monocyte infiltration after myocardial I/R, which opens a new window for using, in combination with endogenous monocyte therapy, to treat AMI.

Resumen: Introducción y objetivos: La quinasa ligada a integrina (ILK) endotelial controla la producción del óxido nítrico, modulando señales de transducción al interior celular. La disminución de ILK endotelial se ha relacionado con la calcificación valvular. Analizamos la asociación de la ILK con la calcificación de la válvula aórtica. Métodos: Estudio observacional, unicéntrico y prospectivo. Recogimos tejido valvular aórtico de pacientes intervenidos de estenosis aórtica, y controles de válvulas no calcificadas. Cuantificamos los niveles de ILK endotelial empleando técnicas de análisis molecular, así como marcadores de crecimiento óseo (BMP2 y RUNX2). Para el control de factores de confusión empleamos regresión logística múltiple por pasos, introduciendo parámetros relacionados con la aterosclerosis y calcificación valvular (edad, DM, HTA, insuficiencia renal). Resultados: Obtuvimos muestras de 75 pacientes y 28 controles. El 69,9% eran varones, la edad media fue de 67 años (DE 9,59 años). Los niveles de ILK fueron significativamente más bajos en válvulas patológicas que en controles (0,96 vs. 0,76; p < 0,001). Existió correlación lineal negativa significativa entre la ILK y la calcificación valvular (coeficiente de Pearson = −0,35; p = 0,002). En el modelo multivariante, ILK presentó una asociación significativa con la calcificación valvular (OR 0,068; p < 0,001), así como la DM (OR 11,80; p = 0,03). Observamos un aumento de marcadores de crecimiento óseo según avanzaba la calcificación, con correlación inversa significativa de ILK y BMP2 (R = −0,417; p < 0,001) y RUNX2 (R = −0,587; p < 0,001). Conclusiones: La disminución de la expresión endotelial de ILK puede influir en la calcificación de la válvula aórtica, marcando el inicio del proceso de transdiferenciación del endotelio valvular a tejido con capacidad osteogénica. Abstract: Introduction and objectives: The endothelial integrin-linked kinase (ILK) controls the production of nitric oxide, modulating transduction signals of mechanical stress in the cell. Decreased endothelial ILK has been related to valve calcification. We analyzed the association of ILK expression with aortic valve calcification. Methods: Observational, single-center and prospective study. Aortic valve tissue samples were obtained from patients whit aortic stenosis, and controls for non-calcified aortic valves. Endothelial ILK levels were quantified using molecular analysis techniques, as well as bone growth markers (BMP2 and RUNX2). Stepwise multiple logistic regression was used to control for confounding factors, introducing clinical parameters related to atherosclerosis and valve calcification (age, DM, HBP, kidney failure). Results: Samples from 75 patients whit aortic stenosis, and 28 controls were obtained. A percentage of 69.9 were men, mean age 67 years (SD 9.59 years). ILK levels were significantly lower in diseased valves than in controls (0.96 vs. 0.76; P < .001). There was a significant negative linear correlation between ILK and degree of valve calcification (Pearson linear correlation coefficient = −0.35; P = .002).In the multivariate model, ILK was significantly associated with valve calcification (OR adjusted 0.068; P < .001), as well as DM (OR 11.80; P = .03). In addition, an increase in bone growth markers was observed as calcification progressed, with a significant inverse correlation between ILK and BMP2 (R = −0.417; P < .001) and RUNX2 (R = −0.587; P < .001). Conclusions: The decrease in the endothelial expression of ILK may influence the calcification of the aortic valve, marking the beginning of the process of transdifferentiation of the valvular endothelium to tissue with osteogenic capacity.

BACKGROUND:Diabetes mellitus (DM) is one of the largest global health emergencies of the 21st century. In recent years, its connection with environmental pollutants, such as bisphenol A (BPA), has been demonstrated; consequently, new structurally similar molecules are used to replace BPA in the plastics industry (BPS, BPF and BPAF). AIM:To carry out a systematic review to allow coherent evaluation of the state of the art. Subsequently, a meta-analysis was performed to unify the existing quantitative data. METHODS:Firstly, a systematic review was carried out, using the terms "(bisphenol) AND (Diabetes OR Hyperglycemia)", to maximize the number of results. Subsequently, three authors analyzed the set of articles. Finally, a meta-analysis was performed for each BP, using RevMan software. In addition, funnel plots were developed to study publication bias. RESULTS:The systematic analysis of the literature revealed 13 recent articles (2017-2023) related to the study paradigm. The qualitative analysis showed interesting data linking diabetes to the three most widely used substitute BPs in the industry: BPS, BPF and BPAF. Finally, the meta-analysis determined a positive relationship with BPS, BPF and BPAF, which was only statistically significant with BPS. CONCLUSION:There is a need to apply the precautionary principle, regulating the use of new BPs. Therefore, replacing BPA with BPS, BPF or BPAF is unlikely to protect the population from potential health risks, such as DM.

Introduction and objectives: The endothelial integrin-linked kinase (ILK) controls the production of nitric oxide, modulating transduction signals of mechanical stress in the cell. Decreased endothelial ILK has been related to valve calcification. We analyzed the association of ILK expression with aortic valve calcification. Methods: Observational, single-center and prospective study. Aortic valve tissue samples were obtained from patients whit aortic stenosis, and controls for non-calcified aortic valves. Endothelial ILK levels were quantified using molecular analysis techniques, as well as bone growth markers (BMP2 and RUNX2). Stepwise multiple logistic regression was used to control for confounding factors, introducing clinical parameters related to atherosclerosis and valve calcification (age, DM, HBP, kidney failure). Results: Samples from 75 patients whit aortic stenosis, and 28 controls were obtained. A percentage of 69.9 were men, mean age 67 years (SD 9.59 years). ILK levels were significantly lower in diseased valves than in controls (0.96 vs. 0.76: P<.001). There was a significant negative linear correlation between ILK and degree of valve calcification (Pearson linear correlation coefficient = -0.35; P=.002).In the multivariate model, ILK was significantly associated with valve calcification (OR adjusted 0.068; P <.001), as well as DM (OR 11.80; P=.03). In addition, an increase in bone growth markers was observed as calcification progressed, with a significant inverse correlation between ILK and BMP2 (R= -0.417; p< .001) and RUNX2 (R= 0.587; P<.001). Conclusions: The decrease in the endothelial expression of ILK may influence the calcification of the aortic valve, marking the beginning of the process of transdifferentiation of the valvular endothelium to tissue with osteogenic capacity. 2022 Sociedad Espanola de Cirugia Cardiovascular y Enclovascular. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC -ND license (http://creativecommons.orgilicensesiby- nc-ncIRLOJ).

Abstract Rationale: Early response after acute myocardial infarction (AMI) is crucial to prevent extensive cardiac necrosis. Interleukin-10 (IL-10) is a key antiinflammatory cytokine, whose expression is closely associated with macrophage polarization towards inflammation resolution. Results: We synthesized NIL10, a micelle-based nanoparticle conjugated to IT9302, a peptide homologue to IL-10 functional domain, with the aim of targeting IL-10 receptor in mice and pigs subjected to AMI. Intravenous administration of 1 mg/kg NIL10 improved the cardiac function of mice and pigs subjected to AMI, as shown by a significant recovery of the left ventricle ejection fraction (LVEF) by days 3 and 7 after AMI, when compared to the levels found in animals injected with NIL10SC, a nanoparticle conjugated with the peptide in a scrambled orientation, in which inflammatory foci and fibrosis were strongly elevated. In IL-10 null mice subjected to AMI, NIL10 also improved heart contractility, while in IL10 receptor deficient animals, NIL10 had no effect. To test whether NIL10 may induce macrophage polarization, M2 macrophage populations were increased after day 3 of reperfusion, in which anti-inflammatory cytokines, including IL4, IL7, IL10, IL13, IL16 and IL27 were also elevated in mice and pigs injected with NIL10. Mechanistically, NIL10 induced activation of the IL-10 receptor/STAT-3 signaling pathway, and STAT3-dependent inhibition of pro-inflammatory NF-kB transcription factor nuclear translocation, as evidenced by inhibition of nuclear p65 in macrophages stimulated with 500 mM LPS in response to incubation with NIL10, and prevented by co-incubation with the STAT-3 pharmacological inhibitor STATTIC, as also evidenced by testing the NF-kB -dependent readout iNOS gene expression with same results. Conclusions: Our findings propose NIL10 nanoparticles as a novel compound to improve cardiac function after myocardial infarction, to preventing cardiac necrosis by inducing polarization toward M2-resolving macrophages, through inhibition of STAT3-induced nuclear translocation of NF-kB.

Calcific aortic valve disease (CAVD) is expected in the aging population. CAVD physiopathology arises from endothelial dysfunction leading to lipid accumulation, inflammation, and osteogenic transformation. Many studies suggest that valve endothelial cells (VECs) undergoing EndMT may differentiate into osteoblastic interstitial cells. We previously showed that Integrin linked kinase (ILK) regulates vasomotor function by preventing endothelial nitric oxide synthase uncoupling. ILK expression in vascular endothelium plays an essential cardioprotective role. Moreover, we have found a significant negative correlation between human valve protein levels of ILK and the osteogenic marker Runx2 and BMP2 in 70 patients with calcific aortic stenosis, a higher decrease at the endothelial level. We hypothesized that Endothelial ILK plays a protective role in human valve endothelial cells osteogenic transition. Isolation of human valve endothelial cells from the aortic (aortic hVECs) and ventricular sides (ventricular hVECs) show a specific ILK decrease in the aortic hVECs from calcific compared to non-calcified valve (p<0.05). Silencing ILK expression in hVECs decreased NO production and increased ROS (Reactive Oxygen Species) production as early as 72 hours. After five days of silencing ILK, hVEC express myofibroblast markers SM22a, α-SMA, MMP12, MMP9, and SNAI 1 while losing the endothelial markers (CD31, and vWF (p<0.01). ILK silenced hVECs (siILK-hVECs) express the osteogenic marker RunX2 indicating osteogenic differentiation and developed calcified nodules. Cell treatment with Noggin, a BMP2 antagonist, did not reverse the increase of Runx2, thus excluding the implication of the BMP2/RUNX2 axis. However, silk-hVECs showed an increase in phosphorylated-SMAD 2, suggesting a TFG-β -dependent mechanism. Treatment of siILK-hVECs with the NO donor DETA-NO decreased Smad 2 activation and RunX2. Moreover, DETA-NO treated siILK hVECs cultured in pro-osteogenic media did not develop calcification. Collectively, our results point to a crucial role of ILK in keeping human valve endothelial cell phenotype preventing valve calcification in a Nitric Oxide-TFGβ1 dependent manner. Financed by the Regional European fund “a way to achieve Europe.” JCCM SBPLY/19/180501/000055S and ISCIII PI20/00930

(1) Background: Early response after acute myocardial infarction (AMI) prevents extensive cardiac necrosis, in which inflammation resolution, including expression of anti-inflammatory interleukin-10 (IL-10), may play a key role. (2) Methods: We synthesized NIL10, a micelle-based nanoparticle, to target IL-10 receptor in mice and pigs subjected to AMI. (3) Results: Administration of NIL10 induced cardiac protection of wild-type and IL-10 knockout mice and pigs subjected to AMI. Cardiac protection was not induced in IL-10-receptor null mice, as shown by a significant recovery of cardiac function, in which inflammatory foci and fibrosis were strongly reduced, together with the finding that resolving M2-like macrophage populations were increased after day 3 of reperfusion. In addition, anti-inflammatory cytokines, including IL-4, IL-7, IL-10, IL-13, IL-16, and IL-27 were also elevated. Mechanistically, NIL10 induced activation of the IL-10 receptor/STAT-3 signaling pathway, and STAT3-dependent inhibition of nuclear translocation of pro-inflammatory NF-ĸB transcription factor. (4) Conclusions: Taken together, we propose using NIL10 as a novel therapeutic tool against AMI-induced cardiac damage.

Introduction: Interleukin-10 (IL-10) has long been recognized as a key anti-inflammatory cytokine, whose expression is associated to macrophage polarization towards resolution after acute myocardial infarction. Hypothesis: Targeting the IL10 receptor (IL10R) in patients undergoing AMI, may represent a new strategy to improve cardiac function. Methods and Results: We synthesized NIL10, a micelle-based nanoparticle conjugated to an IL-10 agonist, to analyze the effect on cardiac function and inflammation resolution after cardiac ischemia/reperfusion. After confirmation of NIL10 (conjugated with Rhodamine) co-localization to IL-10R, as detected by immunohistofluorescence (Fig. 1A), intravenous administration of 1 mg/kg NIL10 in mice and pigs subjected to AMI, efficiently decreased left ventricle fibrosis and significantly improved left ventricle ejection fraction (LVEF), by day 7 after injection, when compared to animals injected with, NIL10SC, a nanoparticle control (Fig. 1B-C). As expected, NIL10 induced macrophage polarization towards M2-like macrophages after day 3 of reperfusion (Fig D), by at least promoting IL-10R activity, as shown by increased phosphorylation of IL-10R and the downstream STAT3 in the necrotic area of the heart (Figure 1E). STAT3-dependent inflammation inhibition was assayed by administration of 50μM NIL10 in RAW-247 cells stimulated with 500 μM LPS, in which nuclear translocation of NF-κB was significantly reduced (Fig. 1E) by at least phosphorylation of I-κB-α. Conclusions: Our findings show NIL10 as a new tool to improve cardiac function in hearts under AMI, at least through inhibition of STAT3-induced nuclear translocation of NF-κB.

Calcific aortic valve disease (CAVD) is highly prevalent during aging. CAVD initiates with endothelial dysfunction, leading to lipid accumulation, inflammation, and osteogenic transformation. Integrin-linked kinase (ILK) participates in the progression of cardiovascular diseases, such as endothelial dysfunction and atherosclerosis. However, ILK role in CAVD is unknown. First, we determined that ILK expression is downregulated in aortic valves from patients with CAVD compared to non-CAVD, especially at the valve endothelium, and negatively correlated with calcification markers. Silencing ILK expression in human valve endothelial cells (siILK-hVECs) induced endothelial-to-mesenchymal transition (EndMT) and promoted a switch to an osteoblastic phenotype; SiILK-hVECs expressed increased RUNX2 and developed calcified nodules. siILK-hVECs exhibited decreased NO production and increased nitrosative stress, suggesting valvular endothelial dysfunction. NO treatment of siILK-hVECs prevented VEC transdifferentiation, while treatment with an eNOS inhibitor mimicked ILK-silencing induction of EndMT. Accordingly, NO treatment inhibited VEC calcification. Mechanistically, siILK-hVECs showed increased Smad2 phosphorylation, suggesting a TGF-β-dependent mechanism, and NO treatment decreased Smad2 activation and RUNX2. Experiments performed in eNOS KO mice confirmed the involvement of the ILK-eNOS signaling pathway in valve calcification, since aortic valves from these animals showed decreased ILK expression, increased RUNX2, and calcification. Our study demonstrated that ILK endothelial expression participates in human CAVD development by preventing endothelial osteogenic transformation.

Introduction: Interleukin-10 (IL-10) has long been recognized as a key anti-inflammatory cytokine, whose expression is associated to macrophage polarization towards resolution after acute myocardial infarction. Hypothesis: Targeting the IL10 receptor (IL10R) in patients undergoing AMI, may represent a new strategy to improve cardiac function. Methods and Results: We synthesized NIL10, a micelle-based nanoparticle conjugated to an IL-10 agonist, to analyze the effect on cardiac function and inflammation resolution after cardiac ischemia/reperfusion. After confirmation of NIL10 (conjugated with Rhodamine) co-localization to IL-10R, as detected by immunohistofluorescence (Fig. 1A), intravenous administration of 1 mg/kg NIL10 in mice and pigs subjected to AMI, efficiently decreased left ventricle fibrosis and significantly improved left ventricle ejection fraction (LVEF), by day 7 after injection, when compared to animals injected with, NIL10SC, a nanoparticle control (Fig. 1B-C). As expected, NIL10 induced macrophage polarization towards M2-like macrophages after day 3 of reperfusion (Fig D), by at least promoting IL-10R activity, as shown by increased phosphorylation of IL-10R and the downstream STAT3 in the necrotic area of the heart (Figure 1E). STAT3-dependent inflammation inhibition was assayed by administration of 50μM NIL10 in RAW-247 cells stimulated with 500 μM LPS, in which nuclear translocation of NF-κB was significantly reduced (Fig. 1E) by at least phosphorylation of I-κB-α. Conclusions: Our findings show NIL10 as a new tool to improve cardiac function in hearts under AMI, at least through inhibition of STAT3-induced nuclear translocation of NF-κB.