Intraplatelet L-Arginine-Nitric Oxide Metabolic Pathway: From Discovery to Clinical Implications in Prevention and Treatment of Cardiovascular Disorders

Abstract

Despite the development of new drugs and other therapeutic strategies, cardiovascular disease (CVD) remains still the major cause of morbidity and mortality in the world population. A lot of research, performed mostly in the last three decades, revealed an important correlation between “classical” demographic and biochemical risk factors for CVD, (i.e., hypercholesterolemia, hyperhomocysteinemia, smoking, renal failure, aging, diabetes, and hypertension) with endothelial dysfunction associated directly with the nitric oxide deficiency. The discovery of nitric oxide and its recognition as an endothelial-derived relaxing factor was a breakthrough in understanding the pathophysiology and development of cardiovascular system disorders. The nitric oxide synthesis pathway and its regulation and association with cardiovascular risk factors were a common subject for research during the last decades. As nitric oxide synthase, especially its endothelial isoform, which plays a crucial role in the regulation of NO bioavailability, inhibiting its function results in the increase in the cardiovascular risk pattern. Among agents altering the production of nitric oxide, asymmetric dimethylarginine—the competitive inhibitor of NOS—appears to be the most important. In this review paper, we summarize the role of L-arginine-nitric oxide pathway in cardiovascular disorders with the focus on intraplatelet metabolism.

Associations between Dietary Animal and Plant Protein Intake and Cardiometabolic Risk Factors—A Cross-Sectional Study in China Health and Nutrition Survey

“…Animal protein provides greater amounts of essential amino acids, such as methionine and lysine, which have been reported to promote hypercholesterolemia in experimental animals [ 49 ]. Conversely, plant protein is rich in nonessential amino acids, including arginine, which may affect hypercholesterolemia via the L-arginine-nitric oxide pathway [ 50 ]. Another proposed mechanism is alteration in gut microbial composition in response to animal compared to plant protein supplementation in both human participants [ 51 ] and experimental animals [ 52 ], concurrently with changes in lipid metabolism.…”

Potential Effects of Soy Isoflavones on the Prevention of Metabolic Syndrome

“…Studies conducted using cultured human aortic vascular endothelial cells revealed that genistein enhances NO production via the PKA/CREB/eNOS/NO signaling pathway and plays a beneficial role in preventing hypertension [ 104 ]. Recent studies have shown the importance of the NO-mediated inhibition of CVDs [ 105 ], suggesting that genistein and daidzein possibly inhibit CVDs by inducing NO production in vascular endothelial cells. In addition, genistein suppressed superoxide production and NOX4 expression via ox-LDL in human umbilical vein endothelial cells [ 106 ].…”

Symmetric Dimethylarginine is Altered in Patients After Myocardial Infarction and Predicts Adverse Outcomes

“… 14 , 15 Furthermore, elevated intraplatelet ADMA concentration may result in impaired platelet-derived NO synthesis and subsequent increase in platelet activity. 16 …”

“…14,15 Furthermore, elevated intraplatelet ADMA concentration may result in impaired platelet-derived NO synthesis and subsequent increase in platelet activity. 16 Next to NOS inhibitors, altered concentrations of NOrelated pathway metabolites may also play a role in endothelial dysfunction. Endothelial isoforms of NOS catalyse the conversion of L-Arg to NO.…”