PKM2-dependent glycolysis promotes the proliferation and migration of vascular smooth muscle cells during atherosclerosis.

PKM2-dependent glycolysis promotes the proliferation and migration of vascular smooth muscle cells during atherosclerosis.
Acta Biochim Biophys Sin (Shanghai). 2019 Dec 23;:
Authors: Zhao X, Tan F, Cao X, Cao Z, Li B, Shen Z, Tian Y
Abstract
Increased glycolysis is involved in the proliferation and migration of vascular smooth muscle cells (VSMCs). Pyruvate kinase isoform M2 (PKM2), a key rate-limiting enzyme in glycolysis, accelerates the proliferation and migration of tumor cells. Although the intracellular mechanisms associated with oxidized low-density lipoprotein (oxLDL)-stimulated VSMC proliferation and migration have been extensively explored, it is still unclear whether oxLDL promotes the proliferation and migration of VSMCs by enhancing PKM2-dependent glycolysis. In the present study, we detected PKM2 expression and pyruvate kinase activity in oxLDL-treated VSMCs and explored the regulation of PKM2 in oxLDL-treated VSMCs and apoE-/- mice. The results showed that PKM2 expression in VSMCs was higher in the intima than in the media in plaques from atherosclerotic rabbits. Moreover, PKM2 level in VSMCs was increased during atherosclerosis progression in apoE-/- mice. Both PKM2 expression and pyruvate kinase activity were found to be upregulated by oxLDL stimulation in VSMCs. Shikonin (SKN), a specific inhibitor of PKM2, was found to inhibit the oxLDL-induced proliferation and migration in VSMCs, in addition to delaying the ather...

Source: Acta Biochimica et Biophysica Sinica - December 22, 2019 Category: Biochemistry Authors: Zhao X, Tan F, Cao X, Cao Z, Li B, Shen Z, Tian Y Tags: Acta Biochim Biophys Sin (Shanghai) Source Type: research