Cardiovascular Drugs and Therapy最新文献

Purpose: Polycystic ovarian syndrome (PCOS) has been associated with cardiovascular risks and comorbid pathologies, particularly cardiorenal disorder. Short-chain fatty acids (SCFAs), especially butyrate, are essential fatty acids that regulate metabolic health and ameliorate granulosa inflammation in PCOS. However, the effect of butyrate on cardiorenal damage associated with PCOS is unknown. This study investigated the impact of SCFA and butyrate on cardiorenal abnormalities in PCOS rat model and the probable involvement of paraoxonase-1 (PON-1).

Methods: Eight-week-old female Wistar rats were allotted into three groups, n = 5, namely control (CTL), PCOS (LEZ), and LEZ + BUT. Induction of PCOS with letrozole (1 mg/kg) lasted for 21 days, while treatment with butyrate (200 mg/kg) commenced after the induction and lasted for 6 weeks uninterruptedly.

Results: PCOS rats showed hyperandrogenism, multiple ovarian cysts, disrupted metabolic indices (fasting insulin and homeostatic model of insulin resistance), and increased (p < 0.05) plasma troponin T, urea, and creatinine, as well as increased cardiac/renal stroma cell-derived factor-1/caspase-6, malondialdehyde/nuclear factor-kappaB, transforming growth factor-β1, and renal ϒ-glutamyl transferase, while a significant decrease (p < 0.05) in systemic nitric oxide/endothelial nitric oxide synthase and cardiac/renal hypoxia-inducible factor-1α and nuclear factor erythroid 2-related factor 2, which were accompanied with a decreased level of PON-1. These systemic and cardiorenal derangements were reversed by butyrate administration.

Conclusions: The results demonstrate the therapeutic benefits of SCFAs, butyrate, against cardiorenometabolic disorder in a model of PCOS. This beneficial effect is accompanied by an elevated level of PON-1. The present data possibly provides a preclinical relevance for the management of cardiorenal syndrome in PCOS.

Purpose: Macrophage-mediated inflammation plays a crucial role in the pathophysiological process of myocardial ischemia/reperfusion (I/R) injury. Recent studies have highlighted the importance of mitochondrial function and inflammasome activation in the inflammatory process. Kirenol, a well-known natural compound, has been shown to regulate inflammation in various diseases. This study investigated whether Kirenol could exert anti-inflammatory effects on macrophages during myocardial I/R injury.

Methods: Mouse myocardial I/R models were established by 45 min of ischemia followed by 24 h of reperfusion. Saline or Kirenol treatment was administered. In vivo assessments included the evaluation of cardiac function, infarcted area, and immune cell infiltration. Subsequently, bone marrow-derived macrophages (BMDMs) were isolated, and mitochondrial function and pyroptosis were assessed. Furthermore, the study compared the cardioprotective effects of Kirenol with a specific NOX1/NOX4 inhibitor, GKT137831.

Results: Kirenol gavage improved cardiac function, decreased infarct area, and alleviated inflammatory infiltration in mice subjected to myocardial I/R injury. Mechanistically, Kirenol inhibited NOX1 and NOX4 and enhanced mitochondrial function, ultimately attenuating the pyroptosis of macrophages. The therapeutic effects of Kirenol and GKT137831 were not significantly different.

Conclusion: This study demonstrates that Kirenol mitigates myocardial I/R injury by inhibiting NOX1 and NOX4, restoring mitochondrial function, and ameliorating macrophage pyroptosis.

Purpose: Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM), and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer.

Methods: Patients ≥ 18 years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new-onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over 2 years from HT initiation.

Results: After propensity score matching, 2155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (OR 0.539, 95% CI 0.446-0.651; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations, and all-cause mortality.

Conclusions: Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal, and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer.

Purpose: The purpose of this study is to compare the incidence of contrast-induced nephropathy (CIN) following percutaneous coronary intervention (PCI) in patients on sodium-glucose cotransporter-2 (SGLT-2) inhibitors prior to the procedure with a matched cohort of patients not receiving sodium-glucose cotransporter-2 inhibitor therapy.

Methods: In this retrospective observational study, patients were eligible for inclusion if they underwent PCI at any of the included study centers within the study time period. Patients were assigned to either the SGLT-2 inhibitor group or control group depending on the documentation of receiving any SGLT-2 inhibitors within 24 h prior to PCI. Propensity matching was utilized to determine the final subjects to include for comparison. The primary outcome was the incidence of CIN.

Results: A total of 192 patients (96 in each group) were matched after exclusion criteria were applied. The incidence of contrast-induced nephropathy was similar between groups, occurring in 8 (8.3%) patients in the SGLT-2 inhibitor group and 6 (6.3%) patients in the comparator group (p = 0.58). There was also no difference between groups in the change in serum creatinine following PCI.

Conclusion: Based on our analysis, we did not identify any risk of CIN associated with SGLT-2 inhibitor use prior to PCI. Based on these results and in conjunction with previously published literature, the use of SGLT-2 inhibitors appears safe prior to PCI. These results still warrant further investigation with prospective adequately powered studies to evaluate the incidence of CIN with SGLT-2 inhibitor use in the setting of PCI.

Implications of epicardial adipose tissue (EAT) on the development of coronary artery disease (CAD) have garnered recent attention. Located between the myocardium and visceral pericardium, EAT possesses unique morphological and physiological contiguity to the heart. The transcriptome and secretome of EAT differ from that of other fat stores in the body. Physiologically, EAT protects the adjacent myocardium through its brown-fat-like thermogenic function and rapid fatty acid oxidation. However, EAT releases pro-inflammatory mediators acting on the myocardium and coronary vessels, thus contributing to the development and progression of cardiovascular diseases (CVD). Furthermore, EAT-derived mesenchymal stromal cells indicate promising regenerative capabilities that offer novel opportunities in cell-based cardiac regeneration. This review aims to provide a comprehensive understanding and unraveling of EAT mechanisms implicated in regulating cardiac function and regeneration under pathological conditions. A holistic understanding of the multifaceted nature of EAT is essential to the future development of pharmacological and therapeutic interventions for the management of CVD.

Advanced glycation end products (AGE), a diverse array of molecules generated through non-enzymatic glycosylation, in conjunction with the receptor of advanced glycation end products (RAGE), play a crucial role in the pathogenesis of diabetes and its associated complications. Recent studies have revealed that the AGE-RAGE axis potentially accelerated the progression of cardiovascular diseases, including heart failure, atherosclerosis, myocarditis, pulmonary hypertension, hypertension, arrhythmia, and other related conditions. The AGE-RAGE axis is intricately involved in the initiation and progression of cardiovascular diseases, independently of its engagement in diabetes. The mechanisms include oxidative stress, inflammation, alterations in autophagy flux, and mitochondrial dysfunction. Conversely, inhibition of AGE production, disruption of the binding between RAGE and its ligands, or silencing of RAGE expression could effectively impair the function of AGE-RAGE axis, thereby delaying or ameliorating the aforementioned diseases. AGE and the soluble receptor for advanced glycation end products (sRAGE) have the potential to be novel predictors of cardiovascular diseases. In this review, we provide an in-depth overview towards the biosynthetic pathway of AGE and elucidate the pathophysiological implications in various cardiovascular diseases. Furthermore, we delve into the profound role of RAGE in cardiovascular diseases, offering novel insights for further exploration of the AGE-RAGE axis and potential strategies for the prevention and management of cardiovascular disorders.