The dynamic change of phenotypic markers of smooth muscle cells in an animal model of cerebral small vessel disease

Abstract

BackgroundThe pathological character of cerebral small vessel disease (CSVD) is the dysfunction of cerebral small arteries caused by risk factors. A switch from the contractile phenotype to the synthetic phenotype of vascular smooth muscle cells (SMCs) can decrease the contractility of arteries. The alteration of the vascular wall extracellular matrix (ECM) is found to regulate the process. We speculated that SMCs phenotype changes may also occur in CSVD induced by hypertension and the alteration of ECM especially fibronectin and laminin may regulate the process. MethodMale spontaneously hypertensive rats (SHR) were used as a CSVD animal model.SMCs phenotypic markers and the ECM expression of the cerebral small arteries of SHR at different ages were evaluated by immunofluorescence. The phenotype changes of primary brain microvascular SMCs cultured on laminin-coating dish or fibronectin-coating dish were evaluated by western blot. ResultA switch from the contractile phenotype to synthetic phenotype in SHR at 10 and 22 weeks of age was observed. Meanwhile, increased expression of fibronectin and a temporary decline of laminin was found in small arteries of SHR at 22 weeks. In vitro experiments also convinced that SMCs cultured on a fibronectin-coating dish failed to maintain contractile phenotype. While at 50 weeks, significant drops of both synthetic and contractile phenotypic markers were witnessed in SHR, with high expressions of four kinds of ECM. ConclusionSMCs in cerebral small arteries exhibited a switch from the contractile phenotype to synthetic phenotype during the chronic process of hypertension and aging. Moreover, the change of fibronectin and laminin may regulate the process.