Abstract
Calcific aortic stenosis is a disorder that impacts the physiology of heart valves. Fibrocalcific events progress in conjunction with thickening of the valve leaflets. Over the years, these events promote stenosis and obstruction of blood flow. Known and common risk factors are congenital defects, aging and metabolic syndromes linked to high plasma levels of lipoproteins. Inflammation and oxidative stress are the main molecular mediators of the evolution of aortic stenosis in patients and these mediators regulate both the degradation and remodeling processes. Mitochondrial dysfunction and dysregulation of autophagy also contribute to the disease. A better understanding of these cellular impairments might help to develop new ways to treat patients since, at the moment, there is no effective medical treatment to diminish neither the advancement of valve stenosis nor the left ventricular function impairments, and the current approaches are surgical treatment or transcatheter aortic valve replacement with prosthesis.
Highlights
Aortic stenosis (AS) is the most frequent heart valvular disease in Western countries and is considered an important public health problem, as confirmed by a long-term study in which the impact of this pathology has been evaluated in 185 countries [1]
Both minimally oxidized low-density lipoprotein (MM-LDL) and lipid oxidation metabolites inhibited proliferation, dose-dependently increased ALP function, and formed extensive areas of calcification in calcifying vascular cells (CVCs) [116]
The results revealed a reduction in matrix calcification due to reduced ALP activity and calcium deposition
Summary
Aortic stenosis (AS) is the most frequent heart valvular disease in Western countries and is considered an important public health problem, as confirmed by a long-term study in which the impact of this pathology has been evaluated in 185 countries [1]. A recent study showed an effect of Lp(a) in the induction of calcification in vitro on HAVICs and an abnormal accumulation of apolipoproteins and phospholipids in diseased valves [30] Given all this evidence on oxidized lipids and AS, the recent sub-study of the ASTRONOMER randomized clinical trial failed to find an association between autoantibody titers (which is an indirect measurement oxidation-specific epitopes) and progression of aortic stenosis or the need for AVR [31]. Another very recent study on CAVS samples revealed elevated Lp(a) and OxPL levels thanks to 18F-sodium fluoride positron emission tomography/computed tomography and, above all, found aortic valve microcalcification before the development of clinical manifestation of the pathology [32]. In addition to these molecular transformations, in this review, we analyzed the role of mitochondria and autophagy in the complex process of aortic calcification
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