Collagen prolyl 4-hydroxylase (C-P4H) is a key enzyme that controls collagen maturation and fibrotic matrix buildup. Cardiac fibrosis is a major pathological basis of many cardiovascular diseases. It is marked by excess collagen deposition and extracellular matrix stiffening, which lead to myocardial stiffness and progression to heart failure. Growing evidence shows that C-P4H and its related subunits are abnormally expressed in several cardiac diseases linked to fibrosis and are closely associated with disease development. C-P4H regulates intracellular procollagen maturation and secretion and thereby indirectly influences extracellular matrix remodeling. Targeting C-P4H has also shown antifibrotic effects in several fibrosis models, which suggests that this enzyme may serve as a potential therapeutic target in cardiac fibrosis. In this review, we briefly summarize the structure and function of C-P4H, discuss its regulatory roles in the development of cardiac fibrosis, and outline the therapeutic prospects of targeting C-P4H.

BACKGROUND:Recombinant human prourokinase (rhPro-UK) is a novel plasminogen activator under investigation for acute pulmonary embolism (aPE). We aimed to explore the efficacy and safety of rhPro-UK vs. alteplase (recombinant tissue plasminogen activator [rt-PA]) in patients with aPE. METHODS:In this phase 2, randomized, single-blind, multicenter, active-controlled, randomized trial involved eighteen centers from university-affiliated tertiary hospitals across China. Patients aged 18-75 years with high or intermediate-to-high risk aPE were randomized to receive intravenous rhPro-UK (40 mg, n = 37; 50 mg, n = 35) or rt-PA (n = 35) and were followed for 7-30 days. The primary efficacy outcome was the change from baseline in systolic pulmonary artery pressure (sPAP) at 24 h post-treatment. Secondary outcomes include changes in right ventricular function parameters. Safety outcomes include all-cause mortality, recurrent PE, hemodynamic deterioration within 7 days, and bleeding events within 30 days. FINDINGS:All treatment groups showed a reduction in sPAP at 24 h (mean change: 40 mg rhPro-UK, -13.40 mmHg [95% confidence interval (CI): -24.10 to -2.71]; 50 mg rhPro-UK, -15.42 mmHg [95% CI: -25.93 to -4.91], and rt-PA: -16.02 mmHg [95% CI: -25.53 to -6.51]), with improvements sustained through 30 days. The incidence of non-major bleeding events was numerically lower in the rhPro-UK groups (40 mg: 63.9%; 50 mg: 55.6%) compared to the rt-PA group (82.9%; p = 0.04). Two deaths occurred, each in the 40 mg rhPro-UK group and rt-PA group. CONCLUSION:rhPro-UK tended to result in early hemodynamic improvement comparable to rt-PA and seemed to have a numerically lower risk of non-major bleeding events. The ClinicalTrials.gov identifier is NCT03108833. FUNDING:This work was funded by Tasly Biopharmaceuticals Co., Ltd.

BACKGROUND:Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is characterized by substantial prognostic and therapeutic heterogeneity. Conventional clinical and anatomical-pathophysiological classifications fail to fully capture these intricacies. Unsupervised clustering approaches such as latent class analysis (LCA) have been used to address this limitation. RESEARCH QUESTION:Can LCA-derived phenogroups refine risk stratification and predict PAH-targeted treatment responses in adult patients with PAH-CHD? STUDY DESIGN AND METHODS:Adult patients with PAH-CHD (N = 889) from a multicenter prospective registry were stratified into post- and pre-tricuspid shunt subsets. LCA was performed in each subset using 28 candidate clinical, laboratory, and hemodynamic variables. Ten-year survival and the effect of PAH-targeted therapy across phenogroups were evaluated. RESULTS:LCA identified 4 phenogroups in each subset with distinct phenotyping patterns. In post-tricuspid shunts, Group 1 ("adaptation with open shunt") exhibited preserved right ventricular function and the best survival despite high afterload. Group 3 ("maladaptation and failure") and Group 4 ("closed shunt and failure") faced 2- to 3-fold higher mortality than Group 1. Notably, Group 2 ("hyperkinetic state") uniquely benefited from combination therapy (Pinteraction = .026). In pre-tricuspid shunts, Group 1 ("high shunt and mild resistance") and Group 3 ("young female and low inflammation") exhibited preserved survival despite varying afterloads. However, Group 2 ("old male and comorbidities") had significantly higher mortality and an attenuated treatment response (Pinteraction = .037) despite sharing mild hemodynamics with Group 1. Group 4 ("high resistance and failure") faced severe hypoxemia and the worst prognosis. INTERPRETATION:LCA successfully stratified patients with PAH-CHD into distinct phenogroups with varied clinical profiles, survival, and treatment responses. This data-driven phenotyping system provides a novel approach for risk stratification and may guide personalized clinical decision-making. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT01417338; URL: www. CLINICALTRIALS:gov.

Background and aims Despite the frequent co-occurrence of frailty and abdominal aortic aneurysm (AAA), it remains unclear whether frailty is a risk factor for the development of AAA. This study aims to determine the association. Methods The study recruited a large-scale cohort from the UK Biobank. The baseline frailty level was assessed through frailty phenotype and frailty index, categorizing participants as non-frail, pre-frail, or frail. The primary outcome was incidence of AAA during follow-up. Cox proportional hazards model was used to explore the association of frailty with AAA risk. The genetic susceptibility was assessed by polygenic risk score. Results A total of 410,606 participants were enrolled in this study. Over a median follow-up of 12.56 years, AAA developed in 692(0.3%), 931(0.5%), and 180(1.0%) participants categorized as non-frail, pre-frail, and frail respectively under the frailty phenotype, while the frailty index revealed 626(0.3%), 873(0.6%), and 304(1.1%) cases across corresponding frailty strata. Compared with the non-frail participants, the risk of AAA was significantly elevated in pre-frail participants (frailty phenotype: HR=1.28, 95%CI=1.16-1.42; frailty index: HR=1.43, 95%CI=1.28-1.59) and frail participants (frailty phenotype: HR=1.82, 95% CI=1.52-2.18; frailty index: HR=2.03, 95%CI=1.74-2.37). The association remained robust in further adjustment of genetic susceptibility and subgroup analysis. Using non-frail participants with low genetic susceptibility as the reference group, those frail participants with high genetic susceptibility demonstrated the greatest hazard for incident AAA, underscoring their synergistic effect on AAA. Conclusions Frailty was longitudinally associated with a high long-term risk of AAA, suggesting frailty as a new independent risk factor for AAA.

Data on the 10-year survival of incident IPAH in China is lacking. The changing trend of characteristics and survival of IPAH over the past decade has yet been demonstrated. The 4-stratum risk model needs further validation in different cohorts. Incident cases of IPAH identified in the national multicenter prospective registry of PAH from 2009 to 2019 were analyzed. Patients with at least two of the three acquired variables (WHO-FC, 6MWD, NT-pro BNP/BNP) were included for risk stratification. 605 incident patients with IPAH were included (age: 35 ± 12 years; 75.2

Background Inflammatory arthritis is recognized to increase cardiovascular disease risk, but its association with degenerative aortic stenosis is not well understood. Methods This prospective cohort study used participants from the UK Biobank, focusing on 4 major types of inflammatory arthritis, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and gout. The primary outcome was the incidence of degenerative aortic stenosis. The primary analysis used Cox proportional hazards models to evaluate the association between inflammatory arthritis and the long‐term risk of degenerative aortic stenosis, as well as to explore potential effect modifiers. Genetic risk was evaluated using polygenic risk scores and self‐reported family history of cardiovascular diseases. Results The study included 497 567 participants, with 271 129 women (54.5%) and 468 015 White individuals (94.1%). The median age was 58 years. Over a median follow‐up of 12.58 years, 4571 cases (0.9%) of degenerative aortic stenosis were identified. Compared with the control group, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and gout were associated with increased risks of degenerative aortic stenosis by 54% (hazard ratio [HR], 1.54 [95% CI, 1.28–1.85]), 72% (HR, 1.72 [95% CI, 1.19–2.50]), 176% (HR, 2.76 [95% CI, 1.43–5.32]), and 36% (HR, 1.36 [95% CI, 1.20–1.54]), respectively. These associations were independent of genetic risk (P for interaction>0.05). Additionally, we identified significant interactions between sex (P for interaction=0.036), age (P for interaction<0.001), and socioeconomic status (P for interaction=0.014) with rheumatoid arthritis, ankylosing spondylitis, and gout on the incidence of degenerative aortic stenosis, respectively. Conclusions Inflammatory arthritis is significantly associated with an increased long‐term risk of degenerative aortic stenosis, underscoring the need for enhanced risk assessment for degenerative aortic stenosis in these populations.

Pulmonary arterial compliance (PAC) reflects the pulsatile load and predicts outcome in pulmonary arterial hypertension (PAH). The prognostic role of PAC in the heterogeneous patient population of PAH associated with congenital heart disease (PAH-CHD) is poorly defined. This study aimed to explore the prognostic value of PAC in patients with PAH-CHD. Adult patients diagnosed with PAH-CHD were collected from a PAH multicenter prospective registry between August 2009 and December 2019. The primary endpoint was all-cause mortality. Multivariable Cox regression and restricted cubic spline (RCS) analysis were used to evaluate the association between PAC and the primary endpoint. Subgroup and interaction analysis between PAC and shunts or defect characteristics were explored. Incremental predictive performance was evaluated by calculating the C-index, continuous net reclassification improvement, and integrated discrimination improvement. A total of 434 adult PAH-CHD patients were enrolled. The median follow-up time was 52.2 months. The survival rate of patients in the lower PAC group was significantly worse than those in the higher PAC group (Log-rank P < 0.001). Multivariable Cox regression analysis showed that PAC independently predicted all-cause mortality after adjustment for other prognostic factors, whether as a continuous variable (HR = 0.665, 95

Background:Ischemic heart disease (IHD) represents the most significant disease burden among all cardiovascular diseases (CVDs). The increasing prevalence of metabolic risks in the 21st century has a profound impact on the disease burden associated with IHD. We analyzed the global, regional, and national burdens of IHD attributable to metabolic risks from 1990 to 2021. Methods:The data were taken from Global Burden of Disease (GBD) study 2021. Deaths, disability-adjusted life years (DALYs), the average annual percent change (AAPC), age-standardized death rates per 100,000 persons (ASDR) and age-standardized rate per 100,000 persons (ASR) of DALYs ranging from 1990 to 2021, were extracted and stratified according to region, nationality, socio-demographic index (SDI), sex, and age. Additionally, the global future trends were predicted using Nordpred prediction model. Results:Compared to 1990, in 2021, the number of death and DALYs from metabolic risk-attributed IHD increased globally by 67.35% and 59.91%, respectively; whereas ASDR and ASR of DALYs showed a decreasing trend and the most severe impact was observed in male and elderly populations. In addition, the burden of disease showed an inverted V-shaped relationship with SDI from 1990 to 2021. AAPC showed a significant increase in developing countries and a decrease in developed countries. We also analyzed the effects of different risk factors including metabolic risk factors on IHD in different SDI regions and genders. The prediction of future disease burden showed that the number of death and DALYs will keep rising, while ASDR and ASR of DALYs will maintain a certain downward trend. Conclusions:The results of this study highlighted the need for screening and intervention for metabolic risk factors in specific regions and populations, this should call for increased collaboration between developing and developed countries to reduce the burden of disease and improve the prognosis of patients with IHD.

AIMS:Heterozygous familial hypercholesterolaemia (HeFH) is a genetic disorder, characterized by high plasma concentrations of low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the efficacy and safety of recaticimab, a new humanized anti-PCSK9 antibody capable of reducing LDL-C levels in patients with poorly controlled HeFH. METHODS AND RESULTS:REMAIN-3 was a multicentre, randomized, double-blind, placebo-controlled Phase 3 study done at 25 sites in China. Patients with a genetic or clinical diagnosis of HeFH, who were on stable lipid-lowering therapy for ≥28 days, had fasting LDL-C ≥ 2.6 mmol/L (or ≥1.8 mmol/L for those with a history of atherosclerotic cardiovascular disease), and had fasting triglyceride ≤5.6 mmol/L, were randomly allocated in a 2:1 ratio to receive subcutaneous recaticimab at 150 mg or matching placebo every 4 weeks for 12 weeks. The primary endpoint was the percentage change in LDL-C from baseline to Week 12. Overall, 143 patients underwent randomization and received recaticimab (n = 95) or placebo (n = 48). At Week 12, the mean percentage change in LDL-C from baseline was -54.4% (95% CI, -57.9 to -50.8%) in the recaticimab group and -4.5% (95% CI, -9.4 to 0.3%) in the placebo group, with a treatment difference of -49.8% (95% CI, -55.8 to -43.9%; P < 0.0001). Recaticimab was superior to placebo in improving other lipid variables, including non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein a. Treatment-related adverse events (TRAEs) were comparable between groups (27.4% with recaticimab vs. 25.0% with placebo). The most common TRAEs occurring more frequently with recaticimab than placebo were injection site reaction (8.4% vs. 0%) and increased blood creatine phosphokinase (5.3% vs. 2.1%). CONCLUSION:Recaticimab significantly lowered the LDL-C level compared with placebo, with an acceptable safety profile, providing a new effective treatment option for patients with inadequately controlled HeFH. REGISTRATION:ClinicalTrials.gov Identifier: NCT04844125.

Background: Biological age (BA) more accurately reflects the true ageing status of the body compared with chronological age. While biological aging is associated with various cardiovascular diseases, the relationship between BA and abdominal aortic aneurysms (AAAs) remains unclear. Methods: This study utilized data from the UK Biobank for analysis. Telomere length (TL) and BA acceleration, calculated using the Klemera-Doubal method (KDM) and phenotypic age (PhenoAge) methods, were used as surrogate measures of biological aging. Cox regression was primarily performed to explore the association between biological aging and AAA risk. Genetic susceptibility was assessed by constructing a polygenic risk score (PRS). Results: This study included 311,646 participants with a median age of 58 years. A total of 1339 new cases of AAA (4.33‰) were reported over a median follow-up period of 12.54 years. Each standard deviation (SD) increase in TL was associated with a 17% decreased risk of AAA (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.79–0.88). Each SD increase in BA acceleration in the KDM was associated with a 21% increased risk (HR = 1.21, 95% CI = 1.12–1.29), and and each SD increase in acceleration in the PhenoAge method was associated with a 40% increased risk (HR = 1.40, 95% CI = 1.32–1.48). These associations were independent of genetic risk, as assessed by the PRS, and a joint effect on AAA occurrence was observed. Additionally, we identified a sex-specific modification in the association between telomere shortening and AAA risk, with a significant association observed exclusively in men. Conclusions: Accelerated biological aging was longitudinally associated with an increased risk of AAA, suggesting that BA may be a significant factor and a potential biomarker for AAA.

Around 70% of patients diagnosed with hypertension exhibit increased levels of renin. SPH3127, an inventive renin inhibitor, has shown favorable tolerability and sustained pharmacodynamic inhibitory impact on plasma renin activity (PRA) during previous phase I trials. This phase II study was conducted to investigate the efficacy and safety of SPH3127 in patients with essential hypertension. This study was conducted in patients with mild to moderate essential hypertension, utilizing a randomized, double-blind, placebo-controlled design. The patients were administered either tablet of SPH3127 at doses of 50 mg, 100 mg, or 200 mg, or a placebo. A total of 122 patients were included in the study, with 121 patients included in the full analysis set. Among these patients, there were 30 individuals in each subgroup receiving different dosage regimens of SPH3127, and 31 patients in the placebo group. The reductions in mean sitting diastolic blood pressure (msDBP) after 8 weeks compared to baseline were 5.7 ± 9.5, 8.6 ± 8.8, and 3.8 ± 10.6 mmHg in the SPH3127 50-, 100-, and 200 mg groups, respectively. In the placebo group, the reduction was 3.1 ± 8.4 mmHg. The corresponding reductions in mean sitting systolic blood pressure (msSBP) were 11.8 ± 13.0, 13.8 ± 11.2, 11.1 ± 13.1, and 7.7 ± 9.7 mmHg in each respective group. SPH3127 is a promising drug for the treatment of patients with essential hypertension. The recommended dosage is 100 mg daily. Clinical trial registration: This study was registered in ClinicalTrials.gov (NCT03756103).

Background: Ischaemia-reperfusion injury (IRI) is the damage that occurs when blood flow is restored to a tissue or organ after a period of ischaemia. Postconditioning is a therapeutic strategy aimed at reducing the tissue damage caused by IRI. Postconditioning in rodents is a useful tool to investigate the potential mechanisms of postconditioning. Currently, there is no convenient approach for postconditioning rodents. Methods: Rats were subjected to a balloon postconditioning procedure. A balloon was used to control the flow in the vessel. This allowed for easy and precise manipulation of perfusion. Evans blue and triphenyltetrazolium chloride (TTC) double staining were used to determine the infarct size. Apoptosis in the myocardium was visualised and quantified by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Western blotting was performed to assess the expression of key apoptotic proteins, i.e., B-cell lymphoma 2 (Bcl-2), Bcl-2 Associated X (Bax), and cleaved caspase-3. Results: The balloon control approach to postconditioning provided accurate control of coronary blood flow and simplified the postconditioning manipulation. Infarct size reduction was observed in IRI rats after post-conditioning. There was a decrease in cardiac apoptosis in IRI rats after conditioning, as detected by TUNEL staining. IRI rats showed increased Bcl-2 levels and decreased Bax and cleaved caspase-3 levels in the myocardium. Conclusions: Postconditioning was successfully applied in rats using this novel approach. Postconditioning with this approach reduced infarct size and apoptosis in the area at risk.

The relationship between sarcopenia and the long-term risk of atrial fibrillation (AF) remains unclear. This study recruited a large prospective Caucasian cohort from the UK Biobank. Participants were assessed at baseline with handgrip strength and muscle mass and were categorized into groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia. Kaplan-Meier method and Cox proportional hazards model were used to explore the association between sarcopenia and the incidence of AF. The genetic predisposition of AF was assessed by polygenic risk score. Sensitivity analyses were performed to validate the results. A total of 384,433 participants with a median age of 58 years and 54.3% women were enrolled in this study. There were 24,007 cases of new-onset AF over a median follow-up of 12.56 years. The groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia accounted for 22,290 (6.1%), 1665 (9.2%), and 52 (11.9%) cases, respectively. Compared with the non-sarcopenia group, participants with probable sarcopenia or confirmed sarcopenia had an 8% (95% CI, 1.03-1.14) or 61% (95% CI, 1.23-2.12) higher risk of AF incidence. The findings remained robust in multiple sensitivity analyses, such as subgroup analysis and further adjustment of genetic predisposition. Notably, the association between sarcopenia and a high AF risk was more pronounced in younger participants, women, and those with valvular heart disease. In conclusion, sarcopenia was associated with a high long-term risk of AF in Caucasians, supporting sarcopenia as a new independent risk factor of AF.

Aims: Mitochondrial homeostasis is essential for maintaining redox balance. Besides canonical autophagy, Rab9-dependent alternative autophagy is a crucial mechanism in metabolic cardiomyopathy. Here, we aim to investigate the role of alternative mitophagy and Beclin 1 haploinsufficiency (Beclin 1(+/-)) in high-fat diet (HFD)-induced metabolic cardiomyopathy. Results: Twenty-four-week HFD impaired glucose tolerance and cardiomyocyte contraction in wild-type mice, both of which were rescued in Beclin 1(+/-) mice. Beclin 1 haploinsufficiency had little effect on the conventional autophagy mediators (ATG5, LC3 II/LC3 I) but further upregulated Rab9 expression, a marker of alternative autophagy, in response to HFD challenge. Furthermore, either the inhibition of alternative autophagy or Beclin 1 haploinsufficiency abolished palmitic acid (PA)-induced cardiomyocyte contractile anomalies. In vitro, PA overactivated mitophagy, resulting in decreased mitochondrial content in H9C2 cells. These aberrations were alleviated in cells deficient in alternative autophagy but not in cells deficient in conventional autophagy. Mechanistically, HFD promoted reactive oxygen species (ROS) production, activated Rab9-dependent alternative mitophagy, and inhibited mitochondrial biosynthesis. Beclin 1(+/-) rescued HFD-induced ROS overflow, mitochondrial biogenesis impairment, and prevented Rab9 translocation from the cytoplasm to the mitochondria, thereby inhibiting Rab9-mediated mitophagy overactivation. Innovation: For the first time, this study suggests that prolonged alternative mitophagy exacerbates chronic HFD-induced cardiac dysfunction and supports the protective role of Beclin 1 haploinsufficiency in metabolic cardiomyopathy. This provides additional evidence for a target-based pharmacological intervention. Conclusion: Beclin 1 haploinsufficiency protects against HFD-induced cardiac dysfunction by inhibiting Rab9-dependent alternative mitophagy and ROS production, while promoting mitochondrial biogenesis. Modulating Beclin 1 expression holds promise in preventing chronic HFD-related cardiomyopathy.

BACKGROUND: The treatment of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains challenging in current clinical practice. AIMS: The study was conducted to investigate a novel biolimus-coated balloon (BCB) for the treatment of coronary DES-ISR compared with the best-investigated paclitaxel-coated balloon (PCB). METHODS: This was a prospective, multicentre, randomised, non-inferiority trial comparing a novel BCB with a clinically proven PCB for coronary DES-ISR. The primary endpoint was in-segment late lumen loss (LLL) at 9 months assessed by an independent core laboratory. Baseline and follow-up optical coherence tomography were performed in a prespecified subgroup of patients. RESULTS: A total of 280 patients at 17 centres were randomised to treatment with a BCB (n=140) versus a PCB (n=140). At 9 months, LLL in the BCB group was 0.23 +/- 0.37 mm compared to 0.25 +/- 0.35 mm in the PCB group; the mean difference between the groups was -0.02 (95% confidence interval [CI]: -0.12 to 0.07) mm; p-value for non-inferiority<0.0001. Similar clinical outcomes were also observed for both groups at 12 months. In the optical coherence tomography substudy, the neointimal area at 9 months was 2.32 +/- 1.04 mm (2) in the BCB group compared to 2.37 +/- 0.93 mm (2) in the PCB group; the mean difference between the groups was -0.09 (95% CI: -0.94 to 0.76) mm (2) ; p=non-significant. CONCLUSIONS: This head-to-head comparison of a novel BCB shows similar angiographic outcomes in the treatment of coronary DES-ISR compared with a clinically proven PCB.

BackgroundPulmonary arterial hypertension (PAH) represents a substantial global risk to human health. This study aims to identify diagnostic biomarkers for PAH and assess their association with the immune microenvironment through the utilization of sophisticated bioinformatics techniques.MethodsBased on two microarray datasets, differentially expressed genes (DEGs) were detected, and hub genes underwent a sequence of machine learning analyses. After pathways associated with PAH were assessed by gene enrichment analysis, the identified genes were validated using external datasets and confirmed in a monocrotaline (MCT)-induced rat model. In addition, three algorithms were employed to estimate the proportions of various immune cell types, and the link between hub genes and immune cells was substantiated.ResultsUsing SVM, LASSO, and WGCNA, we identified seven hub genes, including (BPIFA1, HBA2, HBB, LOC441081, PI15, S100A9, and WIF1), of which only BPIFA1 remained stable in the external datasets and was validated in an MCT-induced rat model. Furthermore, the results of the functional enrichment analysis established a link between PAH and both metabolism and the immune system. Correlation assessment showed that BPIFA1 expression in the MCP-counter algorithm was negatively associated with various immune cell types, positively correlated with macrophages in the ssGSEA algorithm, and correlated with M1 and M2 macrophages in the CIBERSORT algorithm.ConclusionBPIFA1 serves as a modulator of PAH, with the potential to impact the immune microenvironment and disease progression, possibly through its regulatory influence on both M1 and M2 macrophages.

N6-methyladenosine (m6A) is a post-transcriptional epigenetic change with transcriptional stability and functionality regulated by specific m6A-modifying enzymes. However, the significance of genes modified by m6A and enzymes specific to m6A regulation in the context of pulmonary arterial hypertension (PAH) remains largely unexplored. MeRIP-seq and RNA-seq were applied to explore variances in m6A and RNA expression within the pulmonary artery tissues of control and monocrotaline-induced PAH rats. Functional enrichments were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To screen candidate m6A-related genes, the STRING and Metascape databases were used to construct a protein–protein interaction network followed by a real-time PCR validation of their expression. The expression level of an m6A regulator was further investigated using immunohistochemical staining, immunofluorescence, and Western blot techniques. Additionally, proliferation assays were conducted on primary rat pulmonary artery smooth muscle cells (PASMCs). We identified forty-two differentially expressed genes that exhibited either hypermethylated or hypomethylated m6A. These genes are predominantly related to the extracellular matrix structure, MAPK, and PI3K/AKT pathways. A candidate gene, centromere protein F (CENPF), was detected with increased expression in the PAH group. Additionally, we first identified an m6A reader, leucine rich pentatricopeptide repeat containing (LRPPRC), which was downregulated in the PAH rat model. The in vitro downregulation of Lrpprc mediated by siRNA resulted in the enhanced proliferation and elevated expression of Cenpf mRNA in primary rat PASMCs. Our study revealed a modified transcriptome-wide m6A landscape and associated regulatory mechanisms in the pulmonary arteries of PAH rats, potentially offering a novel target for therapeutic strategies in the future.