Vascular smooth muscle cells are impacted considerably by aging, contributing to detrimental age-related remodeling of blood vessel walls in a number of ways. This includes the structural changes that accompany hypertension and atherosclerosis, as well as arterial stiffness and calcification. Insofar as calcification goes, existing evidence supports a role for the inflammatory signaling of senescent cells in driving vascular cells to behave as though they are in bone tissue, depositing calcium. The overall dysfunction of vascular smooth muscle cells is quite complex, however, and probably involves loss of mitochondrial function and other forms of damage beyond that of an inflammatory environment.
Vascular smooth muscle cells (VSMCs) are connected to a network of elastin and collagen fibers. The capacity of the vessel wall to elastically distend is important to accommodate the volume ejected with each heartbeat and to limit peripheral pressure pulsations. The spatial arrangement of VSMCs may influence the mechanical load on the extracellular matrix (ECM) components and, therefore, modulate vessel diameter and stiffness. Chronic exposure to high blood pressure increases tensile stress to which VSMCs respond by proliferation, resulting in hyperplasia and thickening of the vascular wall. Concomitant activity of matrix metallopeptidases facilitates the structural breakdown of elastin ECM, and VSMCs produce collagen ECM, attempting to preserve stiffness homeostasis. High blood pressure thus aggravates age-related stiffening of arteries. Additional ECM disturbances, such as the presence of calcium crystals, have a further impact on the stiffening of the medial layer.
During aging, it is generally accepted that the number of cells in the vasculature decreases, although the causes of this finding remain to be established. It has been hypothesized that VSMCs become senescent and that cell division rates decrease. The recent literature ignores vessel wall cellularity and often refers to cellular processes, such as apoptosis, inflammation, calcification, and epigenetic effects, all playing a part in vessel wall aging. Additionally, with aging, collagen content in major arterial vasculature increases, whereas elastin content decreases and the number of VSMCs declines. As a consequence, remaining VSMCs are embedded in a collagen-enriched ECM with fewer cellular focal adhesions.
Within arterial vessels, differences exist in the content of elastin to VSMC ratios. Large arteries close to the heart contain more elastin and are therefore called "elastic" arteries. It is particularly elastic arteries that stiffen with age. Large artery stiffening results in decreased arterial compliance, especially in those aged over 60 years. Peripheral vessels contain more VSMCs relative to elastin and are termed "muscular" arteries. In muscular arteries, the relative elastin content increases with age, most likely caused by the decline in the number of VSMCs and decreased collagen content. It should be noted that the absolute amount of ECM proteins in the vasculature decreases with age, but that fat and extracellular material, such as calcium crystals, increase. Taken together, the number of VSMCs within the vasculature strongly correlates with vascular stiffening and the arterial remodeling processes.