Large Vessel Cell Heterogeneity and Plasticity: Focus in Aortic Aneurysms

Abstract

Smooth muscle cells and endothelial cells have a remarkable level of plasticity in vascular pathologies. In thoracic and abdominal aortic aneurysms, smooth muscle cells have been suggested to undergo phenotypic switching and to contribute to degradation of the aortic wall structure in response to, for example, inflammatory mediators, dysregulation of growth factor signaling or oxidative stress. Recently, endothelial-to-mesenchymal transition, and a clonal expansion of degradative smooth muscle cells and immune cells, as well as mesenchymal stem–like cells have been suggested to contribute to the progression of aortic aneurysms. What are the factors driving the aortic cell phenotype changes and how vascular flow, known to affect aortic wall structure and to be altered in aortic aneurysms, could affect aortic cell remodeling? In this review, we summarize the current literature on aortic cell heterogeneity and phenotypic switching in relation to changes in vascular flow and aortic wall structure in aortic aneurysms in clinical samples with special focus on smooth muscle and endothelial cells. The differences between thoracic and abdominal aortic aneurysms are discussed.

Nanofiber-based Stretchable Electrodes for Oriented Culture and Mechanotransduction Monitoring of Smooth Muscle Cells

“…Blood vessels are the conduits where blood and tissues exchange oxygen, nutrients, carbon dioxide, and other metabolic wastes and could be grouped into arteries, capillaries, and veins. Structurally, arteries and veins consist of three concentric layers: inner endothelial cell lining, middle smooth muscle cells (SMCs) layer, and an outer layer of fibroblasts and extracellular matrix. – Native blood vessels are permanently exposed to pulsatile stretch, and circumferentially aligned SMCs play an important role in maintaining vascular tone and integrity through active contraction and relaxation. – SMCs possess a contractile phenotype under physiological conditions and can switch to synthetic phenotype for tissue reparation in response to stress or vascular injury, and the phenotypic switching is closely associated with cardiovascular diseases, such as atherosclerosis, vascular calcification, and aortic aneurysms. – At the same time, SMCs can sense mechanical strain and transduce it into a biological response (mechanotransduction) for signal transduction and physiologic regulation of vascular function. , For example, stretch-induced reactive oxygen species (ROS) at a physiological level help SMCs to maintain normal systolic functions, while excessive ROS generation pathologically promotes hypercontractility, abnormal proliferation, and migration of SMCs, exacerbating vascular diseases, such as hypertension and atherosclerosis. Therefore, real-time monitoring of ROS release from contractile SMCs in mechanotransduction is of critical importance to understand their role in vascular regulation. – …”

Wall Shear Stress Predicts Media Degeneration and Biomechanical Changes in Thoracic Aorta

“…Besides extracellular matrix (ECM) components, SMCs have been suggested to regulate aortic stiffness ( Sehgel et al, 2015 ). Recently, multiple SMC phenotypes and immunomodulatory cells were observed in TAA by single-cell RNA-sequencing ( Li et al, 2020 ; Jauhiainen et al, 2022 ). However, the role or location of these cell phenotypes in TAA have remained unknown in relation to WSS or aortic strength ( Jauhiainen et al, 2022 ).…”

“…Recently, multiple SMC phenotypes and immunomodulatory cells were observed in TAA by single-cell RNA-sequencing ( Li et al, 2020 ; Jauhiainen et al, 2022 ). However, the role or location of these cell phenotypes in TAA have remained unknown in relation to WSS or aortic strength ( Jauhiainen et al, 2022 ). In our study, a changed SMC orientation and increased expression of a SMC marker MYH10 were detected in TAV patients.…”

miRNA Regulation of Cell Phenotype and Parietal Remodeling in Atherosclerotic and Non-Atherosclerotic Aortic Aneurysms: Differences and Similarities

“…TAAs and AAAs have different developmental origins as well as pathogenetic factors that induce different structural degeneration of the aortic wall [ 3 ]. Atherosclerosis and chronic inflammation are associated with AAAs [ 3 ], whereas TAAs are characterized by an increased accumulation of proteoglycans [ 4 ]. The histopathological abnormality of TAAs is named cystic medial degeneration, characterized by loss of smooth muscle cells (SMCs) and elastic fiber degeneration that leads to a weakened wall and the consequent high risk of dilatation and aneurysm formation [ 4 , 5 ].…”

“…Atherosclerosis and chronic inflammation are associated with AAAs [ 3 ], whereas TAAs are characterized by an increased accumulation of proteoglycans [ 4 ]. The histopathological abnormality of TAAs is named cystic medial degeneration, characterized by loss of smooth muscle cells (SMCs) and elastic fiber degeneration that leads to a weakened wall and the consequent high risk of dilatation and aneurysm formation [ 4 , 5 ]. Cystic medial degeneration occurs normally with aging, in particular in the presence of hypertension [ 3 ].…”