Rnd3 suppresses endothelial cell pyroptosis in atherosclerosis through regulation of ubiquitination of TRAF6.

Background: As the main pathological basis for various cardiovascular and cerebrovascular diseases, atherosclerosis has become one of the leading causes of death and disability worldwide. Emerging evidence has suggested that Rho GTPase Rnd3 plays an indisputable role in cardiovascular diseases, although its function in atherosclerosis remains unclear. Here, we found a significant correlation between Rnd3 and pyroptosis of aortic endothelial cells (ECs).

Adipsin alleviates cardiac microvascular injury in diabetic cardiomyopathy through Csk-dependent signaling mechanism.

Background: Microvascular complications are associated with an overtly increased risk of adverse outcomes in patients with diabetes including coronary microvascular injury which manifested as disruption of adherens junctions between cardiac microvascular endothelial cells (CMECs). However, particular mechanism leading to diabetic coronary microvascular hyperpermeability remains elusive.

Methods: Experimental diabetes was induced in mice with adipose tissue-specific Adipsin overexpression (Adipsin-Cre) and their respective control (Adipsin).

Fibroblast-specific activation of Rnd3 protects against cardiac remodeling in diabetic cardiomyopathy via suppression of Notch and TGF-β signaling.

Extracellular matrix (ECM) remodeling, a key pathological feature in diabetic cardiomyopathy (DCM), is triggered by oxidative stress, inflammation, and various metabolic disorders in the heart. Cardiac fibroblasts (CFs) are the primary source of ECM proteins and the ultimate effector cells in ECM remodeling. CFs are turned on and differentiated into myofibroblasts in response to profibrotic signaling.

Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis.

As a vital adipokine, Adipsin is closely associated with cardiovascular risks. Nevertheless, its role in the onset and development of cardiovascular diseases remains elusive. This study was designed to examine the effect of Adipsin on survival, cardiac dysfunction and adverse remodeling in the face of myocardial infarction (MI) injury.

Inhibition of macrophage-derived foam cells by Adipsin attenuates progression of atherosclerosis.

Phagocytosis of oxidized low-density lipoprotein (OxLDL) by macrophages yields "foam cells" and serves as a hallmark of atherosclerotic lesion. Adipsin is a critical component of the complement activation pathway. Recent evidence has indicated an obligatory role for Adipsin in pathological models including ischemia-reperfusion and sepsis.

Mst1 Knockout Alleviates Mitochondrial Fission and Mitigates Left Ventricular Remodeling in the Development of Diabetic Cardiomyopathy.

The disruption of mitochondrial dynamics is responsible for the development of diabetic cardiomyopathy (DCM). However, the mechanisms that regulate the balance of mitochondrial fission and fusion are not well-understood. Wild-type, Mst1 transgenic and Mst1 knockout mice were induced with experimental diabetes by streptozotocin injection.

Sirt6-Mediated Endothelial-to-Mesenchymal Transition Contributes Toward Diabetic Cardiomyopathy via the Notch1 Signaling Pathway.

Background: Endothelial-to-mesenchymal transition (EndMT) is an important source of myofibroblasts that directly affects cardiac function in diabetic cardiomyopathy (DCM) via an unknown underlying mechanism. Sirt6 is a member of the Sirtuin family of NAD(+)-dependent enzymes that plays an important role in glucose and fatty acid metabolism. In this study, we investigated whether Sirt6 participates in EndMT during the development of T2DM and the possible underlying regulatory mechanisms.

SHANK3 Co-ordinately Regulates Autophagy and Apoptosis in Myocardial Infarction.

Cardiac remodeling and dysfunction are responsible for the high mortality after myocardial infarction (MI). We assessed the potential for Shank3 to alleviate the post-infarction cardiac dysfunction. The experimental MI mice model was constructed by left anterior descending coronary artery ligation.

Mst1 knockdown alleviates cardiac lipotoxicity and inhibits the development of diabetic cardiomyopathy in db/db mice.

Diabetic cardiomyopathy (DCM) accounts for increasing deaths of diabetic patients, and effective therapeutic targets are urgently needed. Myocardial lipotoxicity, which is caused by cardiac non-oxidative metabolic fatty acids and cardiotoxic fatty acid metabolites accumulation, has gained more attention to explain the increasing prevalence of DCM. However, whether mammalian Ste20-like kinase 1 (Mst1) plays a role in lipotoxicity in type 2 diabetes-induced cardiomyopathy has not yet been illustrated.

Sustained nicorandil administration reduces the infarct size in ST-segment elevation myocardial infarction patients with primary percutaneous coronary intervention.

Objective: Currently, there is still no effective strategy to diminish the infarct size (IS) in patients with ST-segment elevation myocardial infarction (STEMI). According to a previous animal study, nicorandil treatment is a promising pharmaceutical treatment to limit the infarct area. In this study, we aim to investigate the effects of continual nicorandil administration on the IS and the clinical outcomes in patients with STEMI who underwent primary percutaneous coronary intervention (pPCI).

Melatonin protects against diabetic cardiomyopathy through Mst1/Sirt3 signaling.

This study investigated the effects of melatonin on diabetic cardiomyopathy (DCM) and determined the underlying mechanisms. Echocardiography indicated that melatonin notably mitigated the adverse left ventricle remodeling and alleviated cardiac dysfunction in DCM. The mechanisms were attributed to increased autophagy, reduced apoptosis, and alleviated mitochondrial dysfunction.

OSM mitigates post-infarction cardiac remodeling and dysfunction by up-regulating autophagy through Mst1 suppression.

The incidence and prevalence of heart failure (HF) in the world are rapidly rising possibly attributed to the worsened HF following myocardial infarction (MI) in recent years. Here we examined the effects of oncostatin M (OSM) on postinfarction cardiac remodeling and the underlying mechanisms involved. MI model was induced using left anterior descending coronary artery (LAD) ligation.

Melatonin alleviates postinfarction cardiac remodeling and dysfunction by inhibiting Mst1.

Melatonin reportedly protects against several cardiovascular diseases including ischemia/reperfusion (I/R), atherosclerosis, and hypertension. The present study investigated the effects and mechanisms of melatonin on cardiomyocyte autophagy, apoptosis, and mitochondrial injury in the context of myocardial infarction (MI). We demonstrated that melatonin significantly alleviated cardiac dysfunction after MI.

Mst1 inhibits CMECs autophagy and participates in the development of diabetic coronary microvascular dysfunction.

Cardiovascular complications account for a substantial proportion of morbidity and mortality in diabetic patients. Abnormalities of cardiac microvascular endothelial cells (CMECs) lead to impaired cardiac microvascular vessel integrity and subsequent cardiac dysfunction, underlining the importance of coronary microvascular dysfunction. In this study, experimental diabetes models were constructed using Mst1 transgenic, Mst1 knockout and sirt1 knockout mice.

Polydatin protects cardiomyocytes against myocardial infarction injury by activating Sirt3.

Myocardial infarction (MI), which is characterized by chamber dilation and left ventricular (LV) dysfunction, represents a major cause of morbidity and mortality worldwide. Polydatin (PD), a monocrystalline and polyphenolic drug isolated from a traditional Chinese herb (Polygonum cuspidatum), alleviates mitochondrial dysfunction. We investigated the effects and underlying mechanisms of PD in post-MI cardiac dysfunction.

Diagnostic performance of instantaneous wave-free ratio for the evaluation of coronary stenosis severity confirmed by fractional flow reserve: A PRISMA-compliant meta-analysis of randomized studies.

Background: The instantaneous wave-free ratio (iFR) is a new vasodilator-free index of coronary stenosis severity. The aim of this meta-analysis is to assess the diagnostic performance of iFR for the evaluation of coronary stenosis severity with fractional flow reserve as standard reference.

Methods: We searched PubMed, EMBASE, CENTRAL, ProQuest, Web of Science, and International Clinical Trials Registry Platform (ICTRP) for publications concerning the diagnostic value of iFR.

MST1 coordinately regulates autophagy and apoptosis in diabetic cardiomyopathy in mice.

Aims/hypothesis: Diabetic cardiomyopathy (DCM) is associated with suppressed autophagy and augmented apoptosis in the heart although the interplay between the two remains elusive. The ability of mammalian sterile 20-like kinase 1 to regulate both autophagy and apoptosis prompted us to investigate it as a possible candidate in the progression of DCM.

Methods: Wild-type, Mst1 (also known as Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to induce experimental diabetes.

Mst1 participates in the atherosclerosis progression through macrophage autophagy inhibition and macrophage apoptosis enhancement.

Emerging evidence favors the notion that macrophage autophagy plays a prominent role in the pathogenesis of vulnerable plaque, suggesting the therapeutic potential of targeting autophagy in atherosclerosis. Here ApoE(-/-) mice were crossed with Mst1 knockout or Mst1 Tg mice to generate ApoE(-/-):Mst1(-/-) and ApoE(-/-):Mst1Tg mice. All animals were fed high-fat-diet for 4months to induce arterial atherosclerosis.

Roles of Insulin Resistance, Endothelial Dysfunction and Lifestyle Changes in the Development of Cardiovascular Disease in Diabetic Patients.

Background: Diabetes mellitus (DM) caused 1.3 million deaths in 2010, and cardiovascular disease is the leading cause of mortality of diabetic patients. Cardiovascular disease in DM involves complex pathophysiology processes, which are promoted by many risk factors.

Luteolin alleviates post-infarction cardiac dysfunction by up-regulating autophagy through Mst1 inhibition.

Myocardial infarction (MI), which is characterized by chamber dilation and LV dysfunction, is associated with substantially higher mortality. We investigated the effects and underlying mechanisms of Luteolin on post-infarction cardiac dysfunction. Myocardial infarction was constructed by left anterior descending coronary artery ligation.

Safety and Efficacy of Immediate Rotational Atherectomy in Nondilatable Calcified Coronary Lesions Complicated by Coronary Artery Dissection (RAISE).

Objectives: To examine the safety and efficacy of immediate rotational atherectomy (RA) in nondilatable calcified coronary lesions complicated by coronary dissection during percutaneous coronary intervention (PCI).

Background: In the presence of coronary dissection in nondilatable calcified coronary lesions, conservative management is suggested to permit the dissection to heal prior to treatment with RA. However, many patients have frequent angina attacks and some patients develop serious complications during this period.