Abstract
The pathobiology of atherosclerotic disease requires further elucidation to discover new approaches to address its high morbidity and mortality. To date, over 17 million cardiovascular-related deaths have been reported annually, despite a multitude of surgical and nonsurgical interventions and advances in medical therapy. Existing strategies to prevent disease progression mainly focus on management of risk factors, such as hypercholesterolemia. Even with optimum current medical therapy, recurrent cardiovascular events are not uncommon in patients with atherosclerosis, and their incidence can reach 10–15% per year. Although treatments targeting inflammation are under investigation and continue to evolve, clinical breakthroughs are possible only if we deepen our understanding of vessel wall pathobiology. Vascular smooth muscle cells (VSMCs) are one of the most abundant cells in vessel walls and have emerged as key players in disease progression. New technologies, including in situ hybridization proximity ligation assays, in vivo cell fate tracing with the CreERT2-loxP system and single-cell sequencing technology with spatial resolution, broaden our understanding of the complex biology of these intriguing cells. Our knowledge of contractile and synthetic VSMC phenotype switching has expanded to include macrophage-like and even osteoblast-like VSMC phenotypes. An increasing body of data suggests that VSMCs have remarkable plasticity and play a key role in cell-to-cell crosstalk with endothelial cells and immune cells during the complex process of inflammation. These are cells that sense, interact with and influence the behavior of other cellular components of the vessel wall. It is now more obvious that VSMC plasticity and the ability to perform nonprofessional phagocytic functions are key phenomena maintaining the inflammatory state and senescent condition and actively interacting with different immune competent cells.
Highlights
Cardiovascular disease is the leading cause of human morbidity and mortality worldwide, despite improvements and modern approaches to treat and intervene in this condition
This study demonstrated that the expression of ATP-binding cassette transporter 1 (ABCA1) was lower in foam cells originating from human Vascular smooth muscle cells (VSMCs) than in macrophagederived foam cells
This study revealed that IL1b at the stage of advanced plaque development could promote atheroprotective changes via outward remodeling and maintain VSMCs in the fibrous cap [18]
Summary
Cardiovascular disease is the leading cause of human morbidity and mortality worldwide, despite improvements and modern approaches to treat and intervene in this condition. In the CIRT trial, treatment with a broad anti-inflammatory approach did not reduce cardiovascular event rates Taken together, these findings emphasize that we must deepen our understanding of the inflammatory processes that occur in vessel walls and our knowledge of cardiovascular immunology to support the development of therapies that can be used in clinical practice. The intriguing ability of VSMCs to switch phenotypes and acquire properties relevant to different pathological states is complex (Figure 1) This plasticity of VSMCs is driven by biological stimuli from resident or nonresident cells in the vessel wall and is strongly related to the proinflammatory molecular environment. Intriguing data show that macrophage-like VSMCs acting as nonprofessional phagocytes and could lead to a chronic, nonresolving inflammatory state at the site of the vessel wall This process initiates the migration of immune competent cells, including professional phagocytic cells and strong chemokine production [15]. Advanced single-cell technologies and cell lineage tracking should further improve our understanding of these mechanisms [19]
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