Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The arachidonic acid-derived metabolite 12-(S)hydroxyeicosatetraenoic acid (12(S)-HETE), catalyzed by 12-lipoxygenase (12-LOX, ALOX12), exhibits a variety of biological activities with implications in cardiovascular disease. Previous studies have shown higher urinary excretion of this metabolite in essential hypertension. The aim of this study was to analyze the association of polymorphisms in ALOX12 with hypertension and urinary levels of 12(S)-HETE. We studied 200 patients with essential hypertension (aged 56+/-1 years, mean+/-s.e.m., 97 males) and 166 matched controls (aged 54+/-1 years, 91 males). Out of six polymorphisms in the coding region of ALOX12, only R261Q determined a nonconservative amino-acid change and was evaluated by polymerase chain reaction and restriction digestion. Urinary 12(S)-HETE was measured in Sep-Pack-extracted samples using specific enzyme-linked immunosorbent assay. The distribution of genotypes of the R261Q polymorphism was significantly different between patients and controls: patients 92 (0.46) GG, 84 (0.42) GA, 24 (0.12) AA vs controls 56 (0.34) GG, 78 (0.47) GA, 32 (0.19) AA (P=0.030). On the contrary, no association was observed for two intronic polymorphisms. The urinary excretion of 12(S)-HETE (ng/mg creatinine) was significantly higher in GG homozygous patients (13.0+/-1.5) than in GA (8.2+/-1.8) or in AA (8+/-1.5) patients (P=0.018). These results indicate that a nonsynonymous polymorphism in ALOX12 is associated to essential hypertension and to urinary levels of 12(S)-HETE, thus suggesting a role for this gene in this disease.
 ...
PMID:A coding polymorphism in the 12-lipoxygenase gene is associated to essential hypertension and urinary 12(S)-HETE. 1651 35

Vascular aging and essential hypertension cause similar structural and molecular modifications in the vasculature. The 12-lipoxygenase (LO) pathway of arachidonic acid metabolism is linked to cell growth and the pathology of hypertension. Thus, elevated expression of 12-LO has been observed in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). In the present study, we investigated the differences in 12-LO expression and activity between VSMCs from old normotensive Wistar-Kyoto rats (old WKY, 90-week old) and SHR (13-week old). The protein and mRNA expression of basal or angiotensin II (Ang II)-induced 12-LO in old WKY VSMCs were higher than those in SHR VSMCs. The degradation rate of 12-LO mRNA in old WKY VSMCs was slower than that in SHR VSMCs. However, basal or Ang II-induced 12-LO mRNAs in both old WKY and SHR VSMCs decayed more rapidly than that in young WKY (13-week old) VSMCs. Higher expression of 12-LO in old WKY VSMCs than in SHR VSMCs was correlated with the expression level of Ang II subtype 1 receptor (AT(1)R). The reduced levels of nitric oxide (NO) in old WKY and SHR VSMCs compared with young WKY VSMCs were similar, and there was no significant difference in NO production between old WKY and SHR VSMCs transfected with 12-LO siRNA. In addition, in contrast to the proliferation of SHR VSMCs, the proliferation of old WKY VSMCs was not dependent on 12-LO activation. These results suggest that the potential role of 12-LO in normotensive aging vasculature may be different from that in SHR vasculature.
 ...
PMID:Comparison of 12-lipoxygenase expression in vascular smooth muscle cells from old normotensive Wistar-Kyoto rats with spontaneously hypertensive rats. 2287 70