Proportions of Basement Membrane Proteins in Cerebrovascular Smooth Muscle Cells After Exposure to Hypercapnia and Amyloid Beta

Vascular basement membranes (BMs), composed of laminins, collagen IV, fibronectin, and perlecan, are secreted by endothelial cells, pericytes, smooth muscle cells (SMCs), and astrocytes. In the brain, amyloid beta (Aβ) is eliminated along cerebrovascular BMs of capillaries and arteries as intramural periarterial drainage (IPAD). Ageing modifies vascular BMs, impairing IPAD and leading to Aβ deposition as cerebral amyloid angiopathy. To better understand the molecular determinants of IPAD in ageing, we quantified the relative abundance of BMs secreted by human-derived cerebral endothelial cells, pericytes, brain vascular SMCs, and astrocytes in vitro. We then assessed BM protein levels in SMCs under hypercapnia (8% CO₂) as a model of vascular ageing, with and without Aβ exposure. Of the four cell types, we found SMCs secreted the highest levels of fibronectin, laminin, and perlecan, whilst pericytes secreted the highest levels of collagen IV. Hypercapnia increased the expression of collagen IV and fibronectin in SMCs but decreased the expression of laminin. The expression of perlecan increased under hypercapnia, but only in the presence of Aβ. This work highlights the varying compositions of vascular BMs and the dynamic differential responses of SMCs to Aβ and hypercapnia, helping to elucidate the age-related changes that impair IPAD in cerebral vessels.