Interactive contribution of hyperinsulinemia, hyperglycemia, and mammalian target of rapamycin signaling to valvular interstitial cell differentiation and matrix remodeling.

ABSTRACT: Diabetes and its major key determinants insulin resistance and hyperglycemia are known risk factors for calcific aortic valve disease (CAVD). The processes leading to molecular and structural alterations of the aortic valve are yet not fully understood. In previous studies, we could show that valvular interstitial cells (VIC) display canonical elements of classical insulin signaling and develop insulin resistance upon hyperinsulinemia and hyperglycemia accompanied by impaired glucose metabolism. Analyses of cultured VIC and aortic valve tissue revealed extracellular matrix remodeling and degenerative processes. Since PI3K signaling through mammalian target of rapamycin (mTOR) is involved in fibrotic processes of the heart, we aim at further functional investigation of this particular Akt-d

SUBMITTER: Selig JI 

PROVIDER: S-EPMC9661395 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature