Protective role of perivascular adipose tissue in the cardiovascular system.

This review provides an overview of the key role played by perivascular adipose tissue (PVAT) in the protection of cardiovascular health. PVAT is a specific type of adipose tissue that wraps around blood vessels and has recently emerged as a critical factor for maintenance of vascular health. Through a profound exploration of existing research, this review sheds light on the intricate structural composition and cellular origins of PVAT, with a particular emphasis on combining its regulatory functions for vascular tone, inflammation, oxidative stress, and endothelial function. The review then delves into the intricate mechanisms by which PVAT exerts its protective effects, including the secretion of diverse adipokines and manipulation of the renin-angiotensin complex. The review further examines the alterations in PVAT function and phenotype observed in several cardiovascular diseases, including atherosclerosis, hypertension, and heart failure. Recognizing the complex interactions of PVAT with the cardiovascular system is critical for pursuing breakthrough therapeutic strategies that can target cardiovascular disease. Therefore, this review aims to augment present understanding of the protective role of PVAT in cardiovascular health, with a special emphasis on elucidating potential mechanisms and paving the way for future research directions in this evolving field.

Effect of genetically determined BCAA levels on cardiovascular diseases and their risk factors: A Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies have demonstrated that serum branched-chain amino acids (BCAAs) are associated with the risk of various cardiovascular diseases (CVDs) and their risk factors. However, the causal effect is unclear. The aim of this study was to investigate the effect of genetically determined BCAA levels on CVDs and their risk factors using Mendelian randomization (MR). METHODS AND RESULTS: We performed univariable and multivariable MR analyses using summary-level data from multiple GWASs and the FinnGen consortium to investigate the association between BCAA levels and the risk of CVDs (myocardial infarction, ischemic stroke, and intracerebral hemorrhage) and their risk factors (atrial fibrillation, hypertension, heart failure, and valvular heart disease). We used the random-effects IVW approach as the primary statistical method and incorporated MR estimates from different data sources using the fixed-effects model. We found genetically determined total and individual BCAA levels and a high risk of hypertension. However, there is no evidence of a causal relationship between BCAA levels and 3 cardiovascular diseases and other their risk factors. The odds of hypertension increased per 1-SD increase in BCAA levels (OR = 1.02 95% CI: 1.01, 1.04; P = 0.005), valine (OR = 1.02 95% CI: 1.01, 1.03; P<0.0001), leucine (OR = 1.02 95% CI: 1.01, 1.04; P＜0.01), and isoleucine (OR = 1.02 95% CI: 1.01, 1.03; P < 0.0001). This result was also significant in the multivariable MR. CONCLUSIONS: This MR study suggests that total and individual BCAA levels could be associated with a high risk of hypertension.

Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases.

Sestrin2 is a highly conserved protein that can be induced under a variety of stress conditions, including DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and metabolic stress. Numerous studies have shown that the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway has a crucial role in the regulation of metabolism. Sestrin2 regulates metabolism via a number of pathways, including activation of AMPK, inhibition of the mTOR complex 1 (mTORC1), activation of mTOR complex 2 (mTORC2), inhibition of ER stress, and promotion of autophagy. Therefore, modulation of Sestrin2 activity may provide a potential therapeutic target for the prevention of metabolic diseases such as insulin resistance, diabetes, obesity, non-alcoholic fatty liver disease, and myocardial ischemia/reperfusion injury. In this review, we examined the regulatory relationship between Sestrin2 and the AMPK/mTOR signaling pathway and the effects of Sestrin2 on energy metabolism.

Palbociclib improves cardiac dysfunction in diabetic cardiomyopathy by regulating Rb phosphorylation.

Diabetic cardiomyopathy (DCM) is a condition associated with significant structural changes including cardiac tissue necrosis, localized fibrosis, and hypertrophy of cardiomyocytes. This study sought to assess whether and how CDK4/6 inhibitor, Palbociclib, can attenuate DCM using a streptozotocin (STZ)-induced DCM model system. In this study, we found CDK4 and CDK6 expression are significantly increased the cardiac tissue of these mice. Palbociclib treatment after initial STZ administration attenuated oxidative stress and inflammation, thereby reducing cardiomyocyte death and preserving cardiac function in these animals. In addition, Rb phosphorylation induction was found in STZ-treated mice, which was inhibited by Palbociclib treatment. In summary, Palbociclib protects mice from damage associated with DCM pathway activation, making Palbociclib is a relevant therapeutic target in the context of DCM.

CDK4/6 inhibitor protects against myocardial cells apoptosis by inhibiting RB phosphorylation in H9c2 cells.

Cell cycle dysregulation is typical in human cancers, and CDK4/6 inhibitors targeting cell cycle have potential antiapoptosis effect. The aim of this work is to identify the regulatory effect of Palbociclib on apoptosis of H9c2 cells induced by high glucose (HG) and to elucidate the fundamental mechanisms. It was observed that Palbociclib decreased intracellular ROS production, augmented mitochondrial membrane potential and hindered apoptosis of H9c2 cells. Palbociclib increased the Bcl-2/Bax ratio, diminished the expressions of Bax and cleaved-caspase-3, and affected the RB phosphorylation and p53 expression. Altogether, the anti-apoptotic efficacy of Palbociclib could be attributed in part to the modulation of the mitochondria apoptotic pathway.

Successful treatment of a case of acute myocardial infarction due to type A aortic dissection by coronary artery stenting: A case report.

Acute type A aortic dissection (AD) has been recognized as a potentially life threatening condition, which sometimes involves the ostium of the coronary artery and may lead to acute myocardial infarction (AMI). In patients with acute type A AD presenting with clinical signs of AMI, it is crucial to establish the diagnosis rapidly in order to proceed with the correct treatment. The present study reports the diagnosis of a rare case of acute type A AD with the typical presentation of acute inferior MI and cardiogenic shock, which was accidentally diagnosed during catheterization and treated by right coronary ostial occlusion stenting, allowing for further surgical interventions.