Vascular calcification: from the perspective of crosstalk

Abstract

Vascular calcification (VC) is highly correlated with cardiovascular disease morbidity and mortality, but anti-VC treatment remains an area to be tackled due to the ill-defined molecular mechanisms. Regardless of the type of VC, it does not depend on a single cell but involves multi-cells/organs to form a complex cellular communication network through the vascular microenvironment to participate in the occurrence and development of VC. Therefore, focusing only on the direct effect of pathological factors on vascular smooth muscle cells (VSMCs) tends to overlook the combined effect of other cells and VSMCs, including VSMCs-VSMCs, ECs-VMSCs, Macrophages-VSMCs, etc. Extracellular vesicles (EVs) are a collective term for tiny vesicles with a membrane structure that are actively secreted by cells, and almost all cells secrete EVs. EVs docked on the surface of receptor cells can directly mediate signal transduction or transfer their contents into the cell to elicit a functional response from the receptor cells. They have been proven to participate in the VC process and have also shown attractive therapeutic prospects. Based on the advantages of EVs and the ability to be detected in body fluids, they may become a novel therapeutic agent, drug delivery vehicle, diagnostic and prognostic biomarker, and potential therapeutic target in the future. This review focuses on the new insight into VC molecular mechanisms from the perspective of crosstalk, summarizes how multi-cells/organs interactions communicate via EVs to regulate VC and the emerging potential of EVs as therapeutic methods in VC. We also summarize preclinical experiments on crosstalk-based and the current state of clinical studies on VC-related measures.

Aortic calcification accelerates cardiac dysfunction via inducing apoptosis of cardiomyocytes

“…Several studies have identified various factors released from VSMCs in calcification condition, including inflammation, oxidative stress, MMP activity, apoptosis and autophagy, etc 36 . Recently, the discovery of extracellular vesicles secreted during the VC process emphasizes the importance of intercellular/interorgan crosstalks and suggests potentially novel preventive or therapeutic strategies for VC-related diseases 37 . Nevertheless, the specific factors produced in VC contributing to cardiomyocytes apoptosis remain to be determined in future studies.…”

Do Media Extracellular Vesicles and Extracellular Vesicles Bound to the Extracellular Matrix Represent Distinct Types of Vesicles?

“…Extracellular vesicles released by vascular smooth muscle cells are at the sites of medial vascular calcification [152][153][154][155][156][157][158] and can be involved in atherosclerosis-related vascular calcification [151,159]. Extracellular vesicles can communicate with cells and organs to regulate vascular calcification and may serve as therapeutic methods in vascular calcification [160]. In this respect, it is essential to make a clear distinction between matrix vesicles and media vesicles.…”

Identification of Transcripts with Shared Roles in the Pathogenesis of Postmenopausal Osteoporosis and Cardiovascular Disease

“…Several studies have attempted to identify common underlying pathophysiological processes and their respective mediators in order to explain the established link between CVD and OP [8][9][10][11]. A common feature of both diseases appears to be a low-grade chronic state of inflammation which paradoxically promotes bone formation/calcification of the vasculature [12], but also induces decalcification of hard tissue [13]. The calcification occurs both by deposition of calcium and phosphate on elastin and collagen fibrils in vessels via a passive mechanism independent of cellular activity and also by an active process involving inflammation preceding calcification [13].…”