title: Targeting vasoactive peptides for managing calcific aortic valve disease.
abstract: Calcific aortic valve disease (CAVD) represents a spectrum of disease spanning from milder degrees of calcification of valve leaflets, i.e., aortic sclerosis, to severe calcification i.e., aortic stenosis (AS) with hemodynamic instability. The prevalence of CAVD is increasing rapidly due to the aging of the population, being up to 2.8% among patients over 75 years of age. Even without significant aortic valve stenosis, aortic sclerosis is associated with a 50% increased risk of myocardial infarction and death from cardiovascular causes. To date, there is no pharmacological treatment available to reverse or hinder the progression of CAVD. So far, the cholesterol-lowering therapies (statins) and renin-angiotensin system (RAS) blocking drugs have been the major pharmacological agents investigated for treatment of CAVD. Especially angiotensin receptor blockers (ARB)s and angiotensin convertase enzyme inhibitors (ACEI)s, have been under active investigation in clinical trials, but have proven to be unsuccessful in slowing the progression of CAVD. Several studies have suggested that other vasoactive hormones, including endothelin and apelin systems are also associated with development of AS. In the present review, we discuss the role of vasoactive factors in the pathogenesis of CAVD as novel pharmacological targets for the treatment of aortic valve calcification. Key messages Vasoactive factors are involved in the progression of calcific aortic valve disease. Endothelin and renin-angiotensin systems seem to be most prominent targets for therapeutic interventions in the view of valvular pathogenesis. Circulating vasoactive factors may provide targets for diagnostic tools of calcified aortic valve disease.
authors: a Research Unit of Biomedicine, Pharmacology and Toxicology , University of Oulu , Oulu , Finland.
authors: Tuomas
authors: T
authors: Peltonen
authors: a Research Unit of Biomedicine, Pharmacology and Toxicology , University of Oulu , Oulu , Finland.
authors: Pauli
authors: P
authors: Ohukainen
authors: a Research Unit of Biomedicine, Pharmacology and Toxicology , University of Oulu , Oulu , Finland.|b Division of Pharmacology and Pharmacotherapy , University of Helsinki , Finland.
authors: Heikki
authors: H
authors: Ruskoaho
authors: c School of Pharmacy, Faculty of Health Sciences , University of Eastern Finland , Finland.
authors: Jaana
authors: J
authors: Rysä
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D000073861:Apelin / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism; D002114:Calcinosis / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D018450:Disease Progression; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use; D016232:Endothelins / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000401:mortality; D045265:Natriuretic Peptides / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D012084:Renin-Angiotensin System; D012306:Risk
chemical_list: D000073861:Apelin; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D045265:Natriuretic Peptides; D010455:Peptides; D001920:Bradykinin
keywords: Aortic valve stenosis; apelin; bradykinin; endothelin; natriuretic peptides; renin–angiotensin system