No abstract

Cardiovascular diseases (CVDs) are major causes of mortality and morbidity in the modern society. The rupture of atherosclerotic plaque can induce thrombus formation, which is the main cause of acute cardiovascular events. Recently, many studies have demonstrated that there are some relationships between microbiota and atherosclerosis. In this review, we will focus on the effect of the microbiota and the microbe-derived metabolites, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and lipopolysaccharide (LPS), on the stability of atherosclerotic plaque. Finally, we will conclude with some therapies based on the microbiota and its metabolites.

| 4659 wileyonlinelibrary.com/journal/jcmm 1 | INTRODUC TI ON T helpers 17 (Th17) cells have been identified as a new subset of lymphocytes which are shown to promote atherosclerosis (AS), and their associated cytokines in the pathogenesis of AS appear to be contradictory at first glance. 1-3 Recently, growing attention has been paid to the relative contribution of the local vs. peripheral inflammation to the procession of AS. Here, we focused on the communication between peripheral inflammation and vascular inflammation of Th17 cell differentiation during AS.Exosomes are a subset of extracellular vesicles (EVs) released by almost all types of cells, and they play a significant role in cellular proliferation, apoptosis, stress response and differentiation in the initial stage and development of AS. 4,5 In the present study, we investigated exosome-mediated cell-to-cell communication, which induced Th17 cell differentiation and promoted progression of the atherosclerotic plaque. AbstractThe role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137-modified ECs (CD137-Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti-CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo. CD137-Exo efficiently induced the progression of AS in ApoE −/− mice. CD137-Exo increased the proportion of Th17 cells both in vitro and vivo. The IL-6 contained in CD137-Exo which is regulated by Akt and NF-КB pathway was verified to activate Th17 cell differentiation. IL-17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1) and E-selectin in the supernatants of ECs after IL-17 treatment was dramatically increased. CD137-Exo promoted the progression of AS and Th17 cell differentiation via NF-КB pathway mediated IL-6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS. K E Y W O R D S atherosclerosis, endothelial cells; Th17 cells, exosomes

Objective Mechanical damage plays an essential role in the progression of atherosclerosis. Piezo1 is a new mechanically sensitive ion channel. The present study investigated the vascular smooth muscle cells (VSMCs) apoptosis induced by Piezo1 activation and explored its underlying mechanism. Methods We evaluated cell viability and apoptosis rate with cell counting kit-8 (CCK-8) and Annexin V-FITC/PI flow cytometry assay, respectively. And then Western blot was performed to measure the relative protein. Reactive oxygen species (ROS) and intracellular Ca2+ were assessed via fluorescence microscope, and the mitochondrial transmembrane potential was monitored by JC-10 staining. Results Our in vitro study revealed that mice in the ApoE-/- group compared with control mice showed higher Piezo1 expression(P < 0.05). Besides, Yoda1, a Piezo1 agonist, triggered Ca2+ overload, mitochondrial damage, accumulation of ROS, and VSMCs apoptosis in a dose-depend manner. Furthermore, BAPT-AM (an intracellular Ca2+ chelator) and NAC (an antioxidant) suppressed the mitochondrial damage and attenuated the VSMCs apoptosis. Conclusion Our study suggested that Piezo1 induced VSMCs apoptosis because of Ca2+ overload, excessive ROS generation, and mitochondrial dysfunction, which indicated that Piezo1 has potential value in treating vascular diseases.

Angiogenesis, as a process occurring under the regulation of a variety of factors, is one of the important ways of vascular development. It coexists in a variety of pathological and physiological processes. Now a large number of studies have proved that tumor growth, metastasis, and various vascular complications of diabetes are closely related to angiogenesis, and an increasing number of studies have shown that there are many common factors between the two. But angiogenesis is the opposite of the two: it is enhanced in tumors and suppressed in diabetes. Therefore, this review discusses the causes of the phenomenon from the expression of various factors affecting angiogenesis in these two diseases and their effects on angiogenesis in the relevant microenvironment, as well as the application status of these factors or cells as therapeutic targets in the treatment of these two diseases.