title: Caveolin1/protein arginine methyltransferase1/sirtuin1 axis as a potential target against endothelial dysfunction.
abstract: Endothelial dysfunction (ED), an established response to cardiovascular risk factors, is characterized by increased levels of soluble molecules secreted by endothelial cells (EC). Evidence suggest that ED is an independent predictor of cardiac events and that it is associated with a deficiency in production or bioavailability of nitric oxide (NO) and/or an imbalance in the relative contribution of endothelium-derived relaxing and contracting factors. ED can be reversed by treating cardiovascular risk factors, hence, beyond ambiguity, ED contributes to initiation and progression of atherosclerotic disease. Majority of cardiovascular risk factors act by a common pathway, oxidative stress (OS), characterized by an imbalance in bioavailability of NO and reactive oxygen species (ROS). Enhanced ROS, through several mechanisms, alters competence of EC that leads to ED, reducing its potential to maintain homeostasis and resulting in development of cardiovascular disease (CVD). Influential mechanisms that have been implicated in the development of ED include (i) presence of elevated levels of NOS inhibitor, asymmetric dimethylarginine (ADMA) due to augmented enzyme activity of protein arginine methyl transferase-1 (PRMT1); (ii) decrease in NO generation by endothelial nitric oxide synthase (eNOS) uncoupling, or by reaction of NO with free radicals and (iii) impaired post translational modification of protein (PTM) such as eNOS, caveolin-1 (cav1) and sirtuin-1 (SIRT1). However, the inter-related mechanisms that concur to developing ED is yet to be understood. The events that possibly overlay include OS-induced sequestration of SIRT1 to caveolae facilitating cav1-SIRT1 association; potential increase in lysine acetylation of enzymes such as eNOS and PRMT1 leading to enhanced ADMA formation; imbalance in acetylation-methylation ratio (AMR); diminished NO generation and ED. Here we review current literature from research showing interdependent association between cav1-PRMT1-SIRT1 to the outcomes of experimental and clinical research aiming to preserve endothelial function with gene- or pharmaco-therapy.
authors.affiliation: Department of Biotechnology, School of Bioengineering, SRM University, Potheri 603203, Tamil Nadu, India.
authors.forename: Soniya
authors.initials: S
authors.lastname: Charles
authors.affiliation: Medical College Hospital and Research Center, SRM University, Potheri 603203, Tamil Nadu, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Raj
authors.affiliation: Department of Biotechnology, Faculty of Science and Humanities, SRM University, Potheri 603203, Tamil Nadu, India.
authors.forename: Jesu
authors.initials: J
authors.lastname: Arokiaraj
authors.affiliation: Medical College Hospital and Research Center, SRM University, Potheri 603203, Tamil Nadu, India. Electronic address: mkarupiya@gmail.com.
authors.forename: Kanchana
authors.initials: K
authors.lastname: Mala
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D060066:Protein Interaction Maps; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D051242:Caveolin 1; C012427:2-methylarginine; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases; D056564:Sirtuin 1
keywords: 2,6-Diamino-4-pyrimidinol (PubChem CID: 246910); Aspirin (PubChem CID: 2244); BTM-0512 (PubChem CID: 5388063); Caveolin1; Cilostazol (PubChem CID: 2754); Endothelial dysfunction; Endothelial senescence; Pitavastatin (PubChem CID: 5282452); Protein arginine methyltransferase1; Resveratrol (PubChem CID: 445154); SRT1460 (ChemSpider ID:23315250); SRT1720 (PubChem CID: 24180125); SRT2183 (PubChem CID: 24180126); SRT501 (PubChem CID: 445154); Sirtuin1; Splitomicin (PubChem CID: 5269); adenosine dialdehyde (PubChem CID:99920)