Ultrastructural Pathology of Atherosclerosis, Calcific Aortic Valve Disease, and Bioprosthetic Heart Valve Degeneration: Commonalities and Differences

Abstract

Atherosclerosis, calcific aortic valve disease (CAVD), and bioprosthetic heart valve degeneration (alternatively termed structural valve deterioration, SVD) represent three diseases affecting distinct components of the circulatory system and their substitutes, yet sharing multiple risk factors and commonly leading to the extraskeletal calcification. Whereas the histopathology of the mentioned disorders is well-described, their ultrastructural pathology is largely obscure due to the lack of appropriate investigation techniques. Employing an original method for sample preparation and the electron microscopy visualisation of calcified cardiovascular tissues, here we revisited the ultrastructural features of lipid retention, macrophage infiltration, intraplaque/intraleaflet haemorrhage, and calcification which are common or unique for the indicated types of cardiovascular disease. Atherosclerotic plaques were notable for the massive accumulation of lipids in the extracellular matrix (ECM), abundant macrophage content, and pronounced neovascularisation associated with blood leakage and calcium deposition. In contrast, CAVD and SVD generally did not require vasculo- or angiogenesis to occur, instead relying on fatigue-induced ECM degradation and the concurrent migration of immune cells. Unlike native tissues, bioprosthetic heart valves contained numerous specialised macrophages and were not capable of the regeneration that underscores ECM integrity as a pivotal factor for SVD prevention. While atherosclerosis, CAVD, and SVD show similar pathogenesis patterns, these disorders demonstrate considerable ultrastructural differences.

Elements of Immunoglobulin E Network Associate with Aortic Valve Area in Patients with Acquired Aortic Stenosis

“…To our knowledge, relationships between IgE network and acquired AS severity have not been investigated thus far. However, on the basis of the mechanistic similarities between AS and CAD [ 9 , 10 ], as well as previously reported correlations between the severity of CAD and IgE levels [ 6 , 7 , 8 ], we speculated that similar relationships could also be observed in AS.…”

“…Previous studies have demonstrated that the severity of CAD associates with total serum IgE levels [ 6 , 7 , 8 ]. In turn, atherosclerosis shares multiple pathophysiological features and risk factors with aortic (valve) stenosis (AS) [ 9 , 10 , 11 ], the most common acquired heart valve disease, and another chronic vascular inflammatory disorder [ 9 , 12 ]. Therefore, we hypothesized that AS severity may also be related to the IgE network.…”

Expression of tissue inhibitors of metalloproteinases type 1 and type 2 in the leaflets of explanted bioprosthetic heart valves: a new pathogenetic parallel between structural valve degeneration and calcific aortic stenosis

“…Любопытно, что воспаление в створках нативных АК, являющееся движущей силой КАС, также имеет хронический характер [5]. Отложение липидов в створках БПК зарубежных и отечественных моделей ранее уже изучали, хотя точный вклад в структурное разрушение протезного биоматериала до сих пор не установлен [6,15]. Потенциально накопление липидов может способствовать активации окислительных процессов в створках.…”

“…Было продемонстрировано, что биологическая составляющая БПК в значительной степени подвержена разрушению через окислительно-зависимые механизмы [16]. Кроме того, поглощение липидов макрофагами стимулирует перерождение последних в пенистые клетки, которые встречаются в тканях БПК [15]. Пенистые клетки секретируют широкий спектр биоактивных соединений, включающий хемокины, митогены и факторы роста, поэтому они могут стимулировать миграцию фибробластов, их пролиферацию и синтез соединительной ткани.…”

Self-eating and Heart: The Emerging Roles of Autophagy in Calcific Aortic Valve Disease

“…Although not completely the same, CAVD and atherosclerosis show similarities in clinical risk factors, including male sex, smoking habits, hypertension, dyslipidemia, and diabetes [ 3 ] and share common pathological processes associated with endothelial damage, lipoprotein deposition, chronic inflammation, and matrix remodeling [ 4 ]. Historically, CAVD manifests significantly in progressively thickened, fibrosed, and calcified valve cusps.…”