Cardiac Calcifications: Phenotypes, Mechanisms, Clinical and Prognostic Implications

Abstract

There is a growing interest in arterial and heart valve calcifications, as these contribute to cardiovascular outcome, and are leading predictors of cardiovascular and kidney diseases. Cardiovascular calcifications are often considered as one disease, but, in effect, they represent multifaced disorders, occurring in different milieus and biological phenotypes, following different pathways. Herein, we explore each different molecular process, its relative link with the specific clinical condition, and the current therapeutic approaches to counteract calcifications. Thus, first, we explore the peculiarities between vascular and valvular calcium deposition, as this occurs in different tissues, responds differently to shear stress, has specific etiology and time courses to calcification. Then, we differentiate the mechanisms and pathways leading to hyperphosphatemic calcification, typical of the media layer of the vessel and mainly related to chronic kidney diseases, to those of inflammation, typical of the intima vascular calcification, which predominantly occur in atherosclerotic vascular diseases. Finally, we examine calcifications secondary to rheumatic valve disease or other bacterial lesions and those occurring in autoimmune diseases. The underlying clinical conditions of each of the biological calcification phenotypes and the specific opportunities of therapeutic intervention are also considered and discussed.

Atherosclerosis Calcification: Focus on Lipoproteins

“…Although vascular and valvular calcifications share risk factors and molecular pathways, several physio-pathological key differences between these two forms of VC are important to consider [ 15 ]. One of the main differences is linked to the histological structure of calcification sites, with valves consisting of tri-layered structures defined as fibrosa (connective tissue providing strength), spongiosa (mucopolysaccharides facilitating movement), and ventricularis (elastin contributing to flexibility), while vessel walls are constituted mainly by vascular smooth muscle cell (VSMCs) and elastin-rich and connective layers.…”

Agri-Food Waste from Apple, Pear, and Sugar Beet as a Source of Protective Bioactive Molecules for Endothelial Dysfunction and Its Major Complications

“…The mechanical and biological conditions cited above cause the loss of endothelium integrity, leading to lipid, macrophage, and leukocyte infiltration in the subendothelial space, creating the conditions for the formation of atherosclerotic plaques, the main cause of ischemic heart disease and peripheral artery disease. These alterations of the endothelium are also the first step toward calcific aortic valve disease, a pathological condition of the aortic valve, located between the aorta and the left ventricle, which presents an external layer of endothelial cells [ 35 ]. A large body of evidence shows that endothelial dysfunction underlies the severe manifestation of COVID-19 caused by SARS-CoV-2 [ 36 ].…”

LncRNA H19 induces vascular calcification by suppressing the dual-specificity phosphatase 1/optic atrophy protein 1 pathway

“…Vascular calci cation (VC) is very common and can be divided into medial calci cation and intimal calci cation based on the location of the lesion [1][2][3]. Vascular intimal calci cation is one of the main risk factors affecting the prognosis of atherosclerosis, coronary heart disease, diabetes nephropathy and chronic kidney disease [4][5][6]. The mechanism of VC is currently not very clear, and may be related to osteogenic differentiation, apoptosis, calcium and phosphorus deposition, oxidative stress, in ammation, mitochondrial dysfunction in vascular smooth muscle cells (VSMCs) [7,8].…”