Candesartan prevents the progression of arteriopathy in CARASIL model mice.

RNA-seq analysis of pial arteries of 24-month-old wild-type, and candesartan-nontreated and treated HTRA1-KO mice during 4- to 24-month-old. CARASIL is hereditary CSVD caused by loss of HTRA1 protease activity. HTRA1-KO mice accumulated matrisome proteins with fibronectin as a central hub in the intima, and the mice exhibited reduced cerebral blood flow. Candesartan normalized fibronectin accumulation and cerebral blood flow. Our results indicate that arteriopathy in HTRA1-KO mice is due to the accumulation of matrisome proteins with fibronectin as a central hub in the intima, suggesting that these accumulated matrisome proteins may be potential therapeutic targets for CARASIL.