Pulmonary arterial hypertension (PAH) is characterized by muscularized pulmonary blood vessels, leading to right heart hypertrophy and cardiac failure. However, state-of-the-art therapeutics fail to target the ongoing remodeling process. Here, this study shows that matrix metalloproteinases (MMP)-1 and MMP-10 levels are increased in the medial layer of vessel wall, serum, and M1-polarized macrophages from patients with PAH and the lungs of monocrotaline- and hypoxia-induced PAH rodent models. MMP-10 regulates the malignant phenotype of pulmonary artery smooth muscle cells (PASMCs). The overexpression of active MMP-10 promotes PASMC proliferation and migration via upregulation of cyclin D1 and proliferating cell nuclear antigen, suggesting that MMP-10 produced by infiltrating macrophages contributes to vascular remodeling. Furthermore, inhibition of STAT1 inhibits hypoxia-induced MMP-10 but not MMP-1 expression in M1-polarized macrophages from patients with PAH. In conclusion, circulating MMP-10 could be used as a potential targeted therapy for PAH.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial proliferation and remodeling, resulting in a specific increase in right ventricle systolic pressure (RVSP) and, ultimately right ventricular failure. Recent studies have demonstrated that caffeic acid phenethyl ester (CAPE) exerts a protective role in NF-κB-mediated inflammatory diseases. However, the effect of CAPE on PAH remains to be elucidated. In this study, monocrotaline (MCT) was used to establish PAH in rats. Two weeks after the induction of PAH by MCT, CAPE was administrated by intraperitoneal injection once a day for two weeks. Pulmonary hemodynamic measurements and pulmonary artery morphological assessments were examined. Our results showed that administration of CAPE significantly suppressed MCT-induced vascular remodeling by decreasing the HIF-1α expression and PDGF-BB production, and improved in vivo RV systolic performance in rats. Furthermore, CAPE inhibits hypoxia- and PDGF-BB-induced HIF-1α expression by decreasing the activation of the AKT/ERK pathway, which results in the inhibition of human pulmonary artery smooth muscle cells (hPASMCs) proliferation and prevention of cells resistant to apoptosis. Overall, our data suggest that HIF-1α is regarded as an alternative target for CAPE in addition to NF-κB, and may represent a promising therapeutic agent for the treatment of PAH diseases.

Previous studies regarding the cardioprotective effects of dipeptidyl peptidase 4 (DPP-4) inhibitors have not provided sufficient evidence of a relationship between DPP-4 inhibition and actual cardiovascular outcomes. This study aimed to evaluate the impact of DPP-4 inhibitors on the survival of diabetic patients after first acute myocardial infarction (AMI). This was a nationwide, propensity score-matched, case–control study of 186,112 first AMI patients, 72,924 of whom had diabetes. A propensity score, one-to-one matching technique was used to match 2672 controls to 2672 patients in the DPP-4 inhibitor group for analysis. Controls were matched based on gender, age, and a history of hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accident, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention. DPP-4 inhibitors improve the overall 3-year survival rate (log rank P < 0.0001), whether male or female. Cox proportional hazard regression showed DPP-4 inhibitor is beneficial in diabetes patients after AMI (HR = 0.86; 95% CI 0.78–0.95), especially in those patients with hypertension (HR = 0.87; 95% CI 0.78–0.97; P = 0.0103) and cerebrovascular disease (HR = 0.83; 95% CI 0.72–0.97; P = 0.018), but without dyslipidemia (HR = 0.78; 95% CI 0.67–0.92; P = 0.0029), without peripheral vascular disease (HR = 0.86; 95% CI 0.78–0.96; P = 0.0047), without heart failure (HR = 0.84; 95% CI 0.73–0.96; P = 0.0106), without end stage renal disease (HR = 0.86; 95% CI 0.77–0.95; P = 0.0035), and without chronic obstructive pulmonary disease (HR = 0.87; 95% CI 0.78–0.97; P = 0.0096). DPP-4 inhibitor therapy improved long-term survival in diabetic patients after first AMI, regardless of gender.

Although the association between systemic infection and cardiovascular events has been identified, uncertainty remains regarding the incidence and prognosis of sepsis in acute myocardial infarction (AMI). The purpose of this research was to assess the impact of sepsis on survival after first AMI. This was a nationwide cohort study involving the analysis of data from the Taiwan National Health Insurance Research Database for the period 2000-2012, for patients with a primary diagnosis of first AMI. Among the 186112 prospective patients, sepsis was diagnosed in 13065 (7.0%). The propensity score matching technique was used to match 13065 controls to the patients with sepsis and AMI with similar baseline characteristics. Cox proportional hazards regression models, including sepsis, percutaneous coronary intervention (PCI), and comorbidities, were performed to further evaluate the different influences on the mortality risk in patients hospitalized for first AMI. Overall, the 12-year survival rate was lower in AMI patients with sepsis than in those without sepsis (log rank p-value <0.001); this was also shown in the different age and sex groups. The AMI patients with sepsis had a longer length of hospital stay than those without sepsis (32.5days vs. 11.74 days, p<0.001). In the Cox proportional hazards regression analysis, sepsis was an independent risk factor for mortality in patients after AMI (hazard ratio 1.78; 95% confidence interval 1.72-1.83). Interventional management with PCI or coronary artery bypass grafting improved survival in both the sepsis and non-sepsis patients after first AMI. In conclusion, sepsis significantly increased the mortality risk of patients after first AMI. PCI may improve the long-term survival of patients in comparison to those managed conservatively.

Background: The relationship of cardiorespiratory fitness (CRF) with subclinical atherosclerosis affected by the body adiposity has been observed in children, whereas this relationship remains unclear in young adults. Methods and Results: A total of 1520 military recruits, aged 18–40 years, were included in Taiwan in 2018–2020. All subjects underwent detailed physical and blood laboratory examinations. CRF was evaluated by time for a 3000 m run, and subclinical atherosclerosis was evaluated by intima–media thickness of the bulb of the left common carotid artery (cIMT) utilizing high-resolution ultrasonography. Multivariable linear regression analysis with adjustments for age, sex, cigarette smoking, alcohol intake, systolic and diastolic blood pressure, high- and low-density lipoprotein cholesterols, fasting glucose, waist circumference, serum uric acid and serum triglycerides were utilized to determine the correlation between CRF and cIMT. CRF was independently correlated with cIMT (standardized β: 0.11, p < 0.001). Of the cardiometabolic risk markers, serum triglycerides were the only independent risk marker of cIMT (standardized β: 0.063, p = 0.03). In addition, the association of CRF with cIMT did not differ between those with a body mass index (BMI) ≥ 25 kg/m² and those with BMI < 25 kg/m² (standardized β: 0.103 and 0.117; p = 0.01 and 0.005, respectively). Conclusions: In physically active young men and women, there was an inverse association of cIMT with CRF, which was observed in both overweight/mild obesity and normal-weight individuals, highlighting the importance of endurance capacity on reducing risk of early atherosclerosis and implying that the moderation effect of body adiposity might not be present in this population.

Out-of-hospital cardiac arrest (OHCA) is one of the leading causes of death around the world. Bystander cardiopulmonary resuscitation (CPR) is an independent factor to improve OHCA survival. However, the prevalence of bystander CPR remains low worldwide. Community interventions such as mandatory school CPR training or targeting CPR training to family members of high-risk cardiac patients are possible strategies to improve bystander CPR rate. Real-time feedback, hands-on practice with a manikin, and metronome assistance may increase the quality of CPR. Dispatcher-assistance and compression-only CPR for untrained bystanders have shown to increase bystander CPR rate and increase survival to hospital discharge. After return of spontaneous circulation, targeted temperature management should be performed to improve neurological function. This review focuses on the impact of bystander CPR on clinical outcomes and strategies to optimize the prevalence and quality of bystander CPR.