Irisin in atherosclerosis.

Irisin, a novel exercise-induced myokine, has been shown to play important roles in increasing white adipose tissue browning, regulating energy metabolism and improving insulin resistance. Growing evidence suggests a direct role for irisin in preventing atherosclerosis (AS) by inhibiting oxidative stress, improving dyslipidemia, facilitating anti-inflammation, reducing cellular damage and recovering endothelial function. In addition, some studies have noted that serum irisin levels play an essential role in cardiovascular diseases (CVDs) risk prediction, highlighting that irisin has the potential to be a useful predictive marker and therapeutic target of AS, especially in monitoring therapeutic efficacy. This review summarizes the understanding of irisin-mediated regulation in essential biological pathways and functions in atherosclerosis and prompts further exploitation of the biological properties of irisin in the pathogenesis of atherosclerosis.

Angiopoietin-like proteins in atherosclerosis.

Atherosclerosis, as a chronic inflammatory disease within the arterial wall, is a leading cause of morbidity and mortality worldwide due to its role in myocardial infarction, stroke and peripheral artery disease. Additional evidence is emerging that the angiopoietin-like (ANGPTL) family of proteins participate in the pathology of this disease process via endothelial dysfunction, inflammation, dyslipidemia, calcification, foam cell formation and platelet activation. This review summarizes current knowledge on the ANGPTL family of proteins in atherosclerosis related pathological processes. Moreover, the potential value of ANGPTL family proteins as predictive biomarkers in atherosclerosis is discussed. Given the attractive role of ANGPTL3, ANGPTL4, ANGPTL8 in atherosclerotic dyslipidemia via regulation of lipoprotein lipase (LPL), antisense oligonucleotide or/and monoclonal antibody-based inactivation of these proteins represent potential atherosclerotic therapies.

Chemerin in atherosclerosis.

Atherosclerosis (AS), a chronic arterial disease, is characterized by endothelial dysfunction, inflammatory reactions and lipid accumulation in parallel with aberrant angiogenesis and vascular smooth muscle cell (VSMC) proliferation. Adipose tissue has been suggested to have an integral influence on metabolism and endocrine secretion, while there have been increasing concerns about the possible involvement of adipokines in cardiovascular diseases, including AS. Here, we focused on chemerin, an adipokine highly expressed in adipose tissue, with strong evidence of an association with inflammation, endothelial dysfunction, metabolic disorder, aberrant angiogenesis, VSMC proliferation and calcification. In this review, we discuss chemerin and its receptors in the pathogenesis of AS. However, the existing data assign various, even contradictory, roles to chemerin in atherosclerosis, such as inhibiting vascular calcification and impairing endothelial function. Current studies focusing on its anti- and pro-atherogenic effects have pinpointed its distinct role in specific cell types and contexts in the pathogenesis of atherosclerosis. Therefore, the gaps in current knowledge regarding the specific role played by chemerin in the etiology of AS require additional future studies. It seems reasonable to suggest that targeted chemerin therapy can be developed as an innovative approach for treating AS.

Oxidative stress in vascular calcification.

Vascular calcification (VC), which is closely associated with significant mortality in cardiovascular disease, chronic kidney disease (CKD), and/or diabetes mellitus, is characterized by abnormal deposits of hydroxyapatite minerals in the arterial wall. The impact of oxidative stress (OS) on the onset and progression of VC has not been well described. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, xanthine oxidases, myeloperoxidase (MPO), nitric oxide synthases (NOSs), superoxide dismutase (SOD) and paraoxonases (PONs) are relevant factors that influence the production of reactive oxygen species (ROS). Furthermore, excess ROS-induced OS has emerged as a critical mediator promoting VC through several mechanisms, including phosphate balance, differentiation of vascular smooth muscle cells (VSMCs), inflammation, DNA damage, and extracellular matrix remodeling. Because OS is a significant regulator of VC, antioxidants may be considered as novel treatment options.

Adipokines in vascular calcification.

Adipose tissue (AT), a critical endocrine gland, is capable of producing and secreting abundant adipokines. Adipokines act on distant or adjacent organ tissues via paracrine, autocrine, and endocrine mechanism, which play attractive roles in the regulation of glycolipid metabolism and inflammatory response. Increasing evidence shows that adipokines can connect obesity with cardiovascular diseases by serving as promoters or inhibitors in vascular calcification. The chronic hypoxia in AT, caused by the adipocyte hypertrophy, is able to trigger imbalanced adipokine generation, which leads to apoptosis, osteogenic differentiation of vascular smooth muscle cells (VSMCs), vascular inflammation, and abnormal deposition of calcium and phosphorus in the vessel wall. The objectives of this review aim at providing a brief summary of the crucial influence of major adipokines on the formation and development of vascular calcification, which may contribute to better understanding these adipokines for establishing the appropriate therapeutic strategies to counteract obesity-associated vascular calcification.