title: Pleiotropic effects of statins: new therapeutic targets in drug design.
abstract: The HMG Co-enzyme inhibitors and new lipid-modifying agents expand their new therapeutic target options in the field of medical profession. Statins have been described as the most effective class of drugs to reduce serum cholesterol levels. Since the discovery of the first statin nearly 30 years ago, these drugs have become the main therapeutic approach to lower cholesterol levels. The present scientific research demonstrates numerous non-lipid modifiable effects of statins termed as pleiotropic effects of statins, which could be beneficial for the treatment of various devastating disorders. The most important positive effects of statins are anti-inflammatory, anti-proliferative, antioxidant, immunomodulatory, neuroprotective, anti-diabetes, and antithrombotic, improving endothelial dysfunction and attenuating vascular remodeling besides many others which are discussed under the scope of this review. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil-containing protein kinase (ROCK), and their agonistic action on peroxisome proliferator-activated receptors (PPARs) can be viewed as the principle mechanisms underlying the pleiotropic effects of statins. With gradually increasing knowledge of new therapeutic targets of statins, their use has also been advocated in chronic inflammatory disorders for example rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE). In the scope of review, we highlight statins and their pleiotropic effects with reference to their harmful and beneficial effects as a novel approach for their use in the treatment of devastating disorders. Graphical abstract Pleiotropic effect of statins.
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
authors.forename: Onkar
authors.initials: O
authors.lastname: Bedi
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
authors.forename: Veena
authors.initials: V
authors.lastname: Dhawan
authors.affiliation: Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
authors.forename: P L
authors.initials: PL
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology, I.S.F College of Pharmacy, Moga, Punjab, 142001, India. punnubansal79@gmail.com.
authors.forename: Puneet
authors.initials: P
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use; D015195:Drug Design; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000266:history / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D058906:Purinergic P1 Receptor Agonists / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002317:Cardiovascular Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007155:Immunologic Factors; D008055:Lipids; D047492:Peroxisome Proliferator-Activated Receptors; D047428:Protein Kinase Inhibitors; D058906:Purinergic P1 Receptor Agonists; D054460:rho-Associated Kinases; D020830:rac1 GTP-Binding Protein
keywords: Anti-inflammatory; Atherosclerotic; Pleiotropic effects; Rheumatoid arthritis; Statins