Journal of Cardiovascular Pharmacology最新文献

The NC1 domains of collagens have been shown to possess antiangiogenic potential and, therefore, are of therapeutic interest for cancer. However, endostatin and other NC1 domains have not been successful in clinical tests. Therefore, we used evolutionary conservation to perform molecular deconstruction of the domains to further understand their structure-activity relationship, thereby deciphering their antiangiogenic potential. Homology exploration revealed that collagen type X contains a highly interesting NC1 domain (decastatin), with several sequences showing significant homology with vastatin, which is a known collagen type VIII-derived NC1 domain. For comparison, endostatin and vastatin were split into fragments, some of which contained highly conserved regions. The testing of these peptides revealed that the peptides containing conserved regions induced signaling, and fragment four of decastatin showed the highest potency of all fragments, with a calculated IC 50 value of 2.7 μM in the human umbilical vein endothelial cell (HUVEC)-based tube formation assay, which is like that of an intact NC1 domain. Notably, the corresponding fragment from vastatin (V4) also inhibited tube formation, suggesting that this region is of therapeutic interest. In summary, we used evolutionary conservation to identify a novel NC1 domain of collagen type X, a collagen playing a role in angiogenesis of the growth plate. Furthermore, we provided data indicating that the antiangiogenic activity of NC1 domain-derived peptides reside within their conserved domains. As a result, we identified a fragment called Decastatin fragment 4 (D4) derived from the NC1 domain of collagen type X, and which has potent antiangiogenic activity.

The management of antiplatelet therapy in coronary artery disease (CAD) is one of the most debated topics in cardiology. In some clinical scenarios, such as acute coronary syndromes (ACS) and/or percutaneous coronary interventions (PCI), a dual antiplatelet therapy (DAPT) based on the association of a thromboxane A2 (TXA2) pathway inhibitor and a P2Y12 inhibitor is required. Nevertheless, the recent research has been largely focused on the P2Y12 inhibitors, while few data are available on the TXA2 pathway inhibitors, besides aspirin. This gap in the evidence can have relevant clinical implications when aspirin is contraindicated. After years of empirical use, recent clinical studies have shed some light on the efficacy/safety profile of indobufen when compared to aspirin in low-risk CAD patients. However, also encouraged by promising pharmacodynamic data on platelet inhibition, further clinical investigations are strongly advocated.

Acute coronary syndromes (ACS) continue to pose significant challenges for clinical practitioners, particularly regarding the prediction of mid- to long-term outcomes. This study aims to investigate the impact of in-hospital bleeding (IHB) at one-year follow-up in patients admitted for ACS. Data from 23,270 patients enrolled in the international PRAISE registry and discharged after ACS were analyzed. A total of 1,060 patients experienced IHB, while 18,765 did not; 3,445 were excluded due to missing data. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included major bleeding, reinfarction, and composite endpoints at 1 year. Patients with IHB were older, more frequently female, and had a higher prevalence of cardiovascular risk factors (all p < 0.05). At discharge, IHB patients were less likely to receive optimal medical therapy. At the one-year follow-up, all-cause mortality, major bleeding, and reinfarction were significantly higher in the IHB group (all p < 0.001). Bivariate analysis showed a strong association between IHB and all the outcomes of interest (all OR > 1; all p < 0.001). These associations remained significant even after adjusting for several covariates, except for reinfarction (OR 1.3; 95% CI 0.9-2.11; p = 0.149). Age, female sex, hypertension, and peripheral artery disease were found to be independent predictors of IHB, while DES implantation, radial access and left ventricular ejection fraction were identified as protective factors. IHB is a hallmark of frailty in ACS patients; therefore, greater attention should be given during follow-up to patients experiencing this condition.

Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that facilitates the biological metabolism of nitroglycerin. However, no study investigated the association between ALDH2 gene polymorphism and the vasodilation of coronary arteries following intracoronary administration of nitroglycerin. In the present study, we enrolled 427 patients with suspected angina pectoris. ALDH2 genotyping was performed and all patients were given 200 µg nitroglycerin in the right coronary artery during the coronary angiography. The invasive hemodynamic parameters including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were monitored. The reference diameter and stenosis diameter of the right coronary artery were measured with the Stenosis Analysis 1.6 software. Both wild-type and mutant-type groups exhibited significant decreases in SBP, DBP values and increases in HR value after administration of nitroglycerin (P < 0.05). The wild-type group showed significantly higher absolute difference values in SBP when compared to the mutant-type group (P < 0.05). The mutant-type group exhibited significantly lower difference values and rates of change in reference diameter compared to the wild-type group (0.3±0.3 vs. 0.5±0.2, P < 0.001 for the difference value of diameter; 9.6±9.5 vs. 15.8±8.5, P < 0.001 for the rate of change (%)). Conversely, no differences were observed between the wild-type and mutant-type groups in terms of the difference value and rate of change of the stenosis diameter (P > 0.05). In conclusion, ALDH2 gene polymorphism (Glu504Lys) is associated with changes in invasive hemodynamic parameters and coronary artery diameter after intracoronary injection of nitroglycerin.

Hypertension is a major risk factor for cardiovascular disease (CVD), and a major contributor to global morbidity and mortality. In particular, resistant hypertension (rHTN), defined as blood pressure that remains elevated despite treatment with at least three antihypertensive agents including a diuretic, continues to be a major pharmacotherapeutic challenge. Traditional antihypertensive drugs often fail in patients with rHTN, underscoring the need for novel therapies. This is a brief mini-review of aprocitentan, a new drug that promises a glimmer of hope for rHTN patients. This drug is a dual endothelin (ET) receptor antagonist that blocks both ETA and ETB receptors. Given that these two receptors are critical players in vasotone regulation, antagonizing them, such as by aprocitentan, would be expected to significantly reduce blood pressure in patients with rHTN. Indeed, the PRECISION clinical trial demonstrated aprocitentan's superior effectiveness in reducing blood pressure in resistant patients, and the effects were sustained. Aprocitentan has been recently FDA-approved, marking a major milestone in hypertension management, offering hope for patients with difficult-to-treat hypertension.

Cardiovascular diseases are a major cause of death worldwide, and their high incidence poses a significant threat to human health and public health systems. Panax notoginseng, a traditional Chinese medicinal herb with a long history, has shown promise in treating cardiovascular diseases. This review examines the diverse mechanisms through which Panax notoginseng addresses cardiovascular diseases, including anti-inflammatory, antiplatelet aggregation, anticoagulation, anti-oxidative stress, regulation of angiogenesis, antiatherosclerosis, improvement of microcirculatory disorders and protection against myocardial ischemia-reperfusion injury, highlighting saponins as the principal active components. It also summarizes studies involving Panax notoginseng preparations like Xueshuantong and Xuesaitong in treating coronary heart disease and myocardial infarction, and discusses the safety, limitations, and future research directions of these extracts. In conclusion, the cardiovascular protective mechanism of Panax notoginseng is multi-targeted and multi-pathways, and its clinical application is relatively safe, with rare and mild adverse drug reactions, suggesting a promising therapeutic potential.

Abstract: Glucagon-like peptide-1 receptor agonists exhibit beneficial cardiovascular effects. However, the renal effects of different doses of liraglutide in an essential hypertension model have not yet been investigated. Female spontaneously hypertensive rats were treated for 30 days, twice a day, with saline (control) or liraglutide at low (0.06 mg/kg) and high (LH, 0.6 mg/kg) doses. Volume intake and excretion were monitored for a period of 24 hours. In renal tissue, nitrite, nitrate, advanced protein oxidation products, collagen deposition, creatinine (Cr), urea (U), sodium, and potassium were analyzed. Liraglutide reduced body weight gain in both groups. However, in the high dose, it increased urinary volume excretion and sodium/potassium ratio. Both doses reduced the urinary U/Cr ratio and LH increased the serum U/Cr ratio. Advanced protein oxidation products were reduced only in low liraglutide. LH augmented collagen and early markers of kidney injury (blood urea nitrogen, blood urea nitrogen/Cr). LH increased nitrate, reduced nitrite, and caused an aberrant increase in glomerular filtration rate. Both doses' effects were independent of blood pressure and glycemic control. Liraglutide appears to have distinct effects on the hypertensive female kidney depending on the dose, with higher doses impairing kidney function.