Reduction of glyoxalase 1 (GLO1) aggravates cerebrovascular remodeling via promoting the proliferation of basilar smooth muscle cells in hypertension.

Uncontrollable vascular smooth cell proliferation is responsible for vascular remodeling during hypertension development. Glyoxalase 1 (GLO1), the major enzyme detoxifying methylglyoxal, has a critical role in regulating proliferation of several cell types. However, little is known whether GLO1 is involved in cerebrovascular remodeling and basilar smooth muscle cell (BASMC) proliferation during hypertension. Here we explored the role of GLO1 in angiotensin II (Ang II)-induced cerebrovascular remodeling and proliferation of BASMCs and the underlying mechanisms. The protein expression of GLO1 in basilar arteries from hypertensive mice was decreased, and GLO1 expression was negatively correlated with medial cross-sectional area and blood pressure in basilar arteries during hypertension. Knockdown of GLO1 promoted while overexpression of GLO1 prevented Ang II-induced cell proliferation and cell cycle transition in BASMCs. These results were related to the inhibitory effects of GLO1 on PI3K/AKT/CDK2 cascade activation upon Ang II treatment. In addition, in vivo study, GLO1 overexpression with adeno-associated virus harboring GLO1 cDNA improved cerebrovascular remodeling in basilar artery tissue during Ang II-induced hypertension development. These data indicate that GLO1 reduction mediates cerebrovascular modeling via PI3K/AKT/CDK2 cascade-dependent BASMC proliferation. GLO1 acts as a negative regulator of hypertension-induced cerebrovascular remodeling and targeting GLO1 may be a novel therapeutic strategy to prevent hypertension-associated cardiovascular complications such as stroke.

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