Pathophysiological Role of Adiponectin, Leptin and Asymmetric Dimethylarginine in the Process of Atherosclerosis

Abstract

Adipose tissue is recognized as a rich source of proinflammatory mediators that may directly contribute to vascular injury, insulin resistance, and atherogenesis. Many studies have shown that adiponectin has antiatherogenic and anti-inflammatory properties. Adiponectin acts not only as a factor increasing insulin sensitivity, and the protective effect may result from its ability to suppress production of proinflammatory cytokines. It negatively regulates the expression of TNF-alpha and C-reactive protein (CRP) in adipose tissue; reduces expression of vascular and intracellular adhesion molecules (VCAM-1, ICAM-1), E-selectin, interleukin-8 (IL-8). Hyperleptinemia has been linked with the development of hypertension and endothelial dysfunction/atherosclerosis, two main pathophysiological conditions associated with cardiovascular disease development. Leptin-mediated increases in sympathetic nervous system activity may be among the principal mechanisms evoking obesity related hypertension. Leptin stimulates the secretion of proinflammatory cytokines, and increases the release of endothelin-1 (ET-1), which may promote hypertension. Increased serum levels of asymmetric dimethylarginine (ADMA), a physiological regulator of the biosynthesis of nitric oxide (NO), promote the process of atherosclerosis, leading to the occurrence of endothelial dysfunction and cardiovascular disease.

Serum Metrnl is associated with the presence and severity of coronary artery disease

“…These proteins are known under the term “adipokines,” for example, adiponectin, leptin, resistant, visfatin, retinol‐binding protein 4, etc., which are involved in the pathophysiology of obesity and insulin resistance and therefore have indirect effects on atherosclerosis . For instance, adiponectin is an adipose tissue‐derived adipokine which has protective role in the initiation and progression of atherosclerosis through its anti‐inflammatory and antiatherogenic effects . Leptin exerts various atherogenic effects such as induction of endothelial dysfunction, stimulation of inflammatory reaction and oxidative stress, decrease in paraoxonase activity, platelet aggregation, etc .…”

Epigallocatechin Gallate (EGCG) Improves Anti-Angiogenic State, Cell Viability, and Hypoxia-Induced Endothelial Dysfunction by Downregulating High Mobility Group Box 1 (HMGB1) in Preeclampsia

“…NO is mainly catalyzed and produced by eNOS, which has the function of vasodilatation and protecting vascular endothelium under physiological contents [ 25 , 26 ]. Accumulating evidence has suggested that intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), endothelin 1 (ET-1), and E-selectin play pivotal roles in the mechanisms of endothelial dysfunction [ 27 , 28 ]. In the present study, the expression of ICAM-1, VCAM-1, ET-1, and E-selectin was upregulated and the levels of NO and eNOS were downregulated in HUVECs cultured with culture medium of hypoxic JEG-3 cells.…”

Role of Renin-Angiotensin System Components in Atherosclerosis: Focus on Ang-II, ACE2, and Ang-1–7

“…As previously reviewed by us and by others, atherosclerosis consists of an inflammatory response of arterial wall to injuries. This inflammation is often initiated by endothelial dysfunction and progresses to cellular adhesion molecules (CAM) expression, adhesion of circulating leukocytes to the endothelial cells (Koleva et al, 2016), leucocyte migration and the formation of a fibrous cap around a lipidic core, which compromises vascular lumen (Freitas-Lima et al, 2015). In addition to its traditional role in hypertension, the long-term blood pressure control system (the renin-angiotensin system -RAS) is directly involved in the development of atherosclerotic lesions due to its mainly effects on endothelial function, inflammation, fibrosis, coagulation balance, plaque stability, and structural remodeling (Montezano et al, 2014;Husain et al, 2015).…”