Pathological Evidence From an Experimental Rat Model Demonstrates That Aortic Hypoperfusion Contributes to the Development of Medial Arterial Calcification

TL;DR

This study shows that reduced blood flow in rat aortas leads to arterial calcification by damaging the aortic wall and creating conditions for calcium deposits.

Contribution

The study identifies aortic hypoperfusion as a novel initiating factor for medial arterial calcification.

Findings

Severe hypoperfusion increases calcium deposition in the aortic media.

Elastic fiber flattening and medial cell death occur before calcium phosphate deposition.

Microvoids formed after cell death act as scaffolds for calcification.

Abstract

Medial arterial calcification, ectopic deposition of calcium phosphate crystals in the media, causes aortic stiffness which is associated with the mortality of cardiovascular diseases. Previous studies clarified several factors which are related to disease progression processes, on the contrary, inducing factors of medial arterial calcification remain obscure. In this study, we performed pathological analyses of the aorta in an experimental animal model under the condition of hypoperfusion to understand unexplored events underlying medial arterial calcification. The area of calcium deposition varied with the severity of hypoperfusion, and the extent of calcium deposition was highest under conditions of severe hypoperfusion. Thinning of the media, destruction of elastic fibers, and increased transformation marker of vascular smooth muscle cells into osteoblast‐like cells were observed earlier than calcium deposition. Time‐dependent observations of the hypoperfusion‐induced aorta show the flattening of elastic fibers and death of medial cells prior to calcium phosphate deposition, followed by the formation of microvoids which were used as scaffolds for calcium phosphate crystal formation. These data showed that aortic wall hypoperfusion can be an initiating factor of calcium phosphate deposition in the arterial media.

Time‐dependent observations of the hypoperfusion‐induced aorta show the flattening of elastic fibers and death of medial cells prior to calcium phosphate deposition, followed by the formation of microvoids which were used as scaffolds for calcium phosphate crystal formation. These data showed that aortic wall hypoperfusion can be one of the initiating factors of calcium phosphate deposition in the arterial media.

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