Homocysteine and Hypertension in Diabetes: Does PPARγHave a Regulatory Role?

Abstract

Dysfunction of macro- and microvessels is a major cause of morbidity and mortality in patients with cardio-renovascular diseases such as atherosclerosis, hypertension, and diabetes. Renal failure and impairment of renal function due to vasoconstriction of the glomerular arteriole in diabetic nephropathy leads to renal volume retention and increase in plasma homocysteine level. Homocysteine, which is a nonprotein amino acid, at elevated levels is an independent cardio-renovascular risk factor. Homocysteine induces oxidative injury of vascular endothelial cells, involved in matrix remodeling through modulation of the matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) axis, and increased formation and accumulation of extracellular matrix protein, such as collagen. In heart this leads to increased endothelial-myocyte uncoupling resulting in diastolic dysfunction and hypertension. In the kidney, increased matrix accumulation in the glomerulus causes glomerulosclerosis resulting in hypofiltration, increased renal volume retention, and hypertension. PPARγ agonist reduces tissue homocysteine levels and is reported to ameliorate homocysteine-induced deleterious vascular effects in diabetes. This review, in light of current information, focuses on the beneficial effects of PPARγ agonist in homocysteine-associated hypertension and vascular remodeling in diabetes.

Effects of Isolated Vitamin B6 Supplementation on Oxidative Stress and Heart Function Parameters in Experimental Hyperhomocysteinemia

“…This finding might be suggestive of diastolic dysfunction, probably by the HcyT effect of increased endothelial-myocyte uncoupling, resulting in hypertension 39 . E/A ratio was increased in the Hcy group compared to the CB 6 group.…”

A Correlative Study of Serum Homocysteine with Serum Lipid Profile in Young Adult Hypertensive Patients in Indian Population

“…The present study has also shown the positive correlation between serum homocysteine and total cholesterol, Triglyceride, LDL cholesterol & negative correlation between serum homocysteine and HDL cholesterol in hypertensive subjects. Hyperhomocysteinemia, through its oxidative effects could reduce vasodilators like nitric oxide as well as promote extracellular matrix accumulation and smooth muscle cell proliferation, leading to vascular constriction and stiffness 36,37 . The atherogenicity of homocysteine may involve several mechanisms including LDLcholesterol oxidative modification, and HDL-cholesterol decrease 38 .…”

Functional Polymorphism rs13306560 of the MTHFR Gene Is Associated With Essential Hypertension in a Mexican-Mestizo Population

“…13,14 It has been proposed that hyperhomocysteinemia induces oxidative injury of vascular endothelial cells, arteriolar constriction, renal dysfunction, and increased sodium reabsorption. [15][16][17] Results of 2 meta-analyses suggest that the MTHFR C677T polymorphism is associated with an increased risk of hypertension, at least in Asian and white populations. 18,19 Our group previously found that the 677TT genotype is associated with a reduced risk of preeclampsia in Maya-Mestizo women.…”