Vascular muscle turns into plaque fuel
Atherosclerosis grows partly through a surprising mechanism. Smooth muscle cells in the vessel wall change their identity and start behaving like immune cells. In doing so, they accelerate the growth of the narrowing from within.
Atherosclerosis is the leading cause of death worldwide. A plaque is essentially an accumulation of dead immune cells, fat particles, and connective tissue in the vessel wall. What has long been underestimated is that smooth muscle cells of blood vessels also actively contribute to that growth. They transform from contractile cells (which regulate blood pressure) into cells that closely resemble macrophages, the immune cells that normally attempt to clear the plaque. The researchers describe this as a form of cellular reprogramming, driven by the toxic environment inside the plaque.
A self-reinforcing growth mechanism
The transformed muscle cells do not behave like healthy macrophages: they do not clear the plaque, but add mass to the growing accumulation. They also secrete inflammatory signals that attract more immune cells. This makes it a self-reinforcing process, which is why comparisons to tumour growth are not entirely misplaced.
Modern techniques such as single-cell omics (the analysis of individual cells) have revealed greater variation in this behaviour than previously recognised. Some muscle cells shift towards a fibroblast-like profile (connective tissue cell), others towards a macrophage profile. That heterogeneity partly determines whether a plaque remains stable or ruptures, since rupture is the direct cause of a heart attack or stroke.
Implications for treatment
The review, published as part of ongoing cardiovascular research, discusses strategies to inhibit this cellular transformation. These include drugs that block the molecular signals triggering the switch, and nanotechnology that delivers specific agents to the plaque. Large clinical studies demonstrating that inhibiting this transformation actually prevents heart attacks are still lacking. The findings are, for now, promising as a direction for future research.
The relevance to aging is clear: plaque growth increases with age, and the capacity of cells to maintain their normal identity declines. Understanding why smooth muscle cells change character is also understanding why aging makes the heart vulnerable.
Search terms for further research: vascular smooth muscle cell phenotypic plasticity, atherosclerosis cellular reprogramming macrophages, plaque rupture cell identity aging