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【medical-news】抗衰老基因可有效降低高血压
Persistent hypertension, or high blood pressure, is a risk factor for stroke, heart attack, heart failure, arterial aneurysm and is the leading cause of chronic kidney failure. Even a modest elevation of arterial blood pressure leads to shortened life expectancy.
Researchers, led by principal investigator Zhongjie Sun, tested the effect of an anti-aging gene called klotho on reducing hypertension. They found that by increasing the expression of the gene in laboratory models, they not only stopped blood pressure from continuing to rise, but succeeded in lowering it. Perhaps most impressive was the complete reversal of kidney damage, which is associated with prolonged high blood pressure and often leads to kidney failure.
"One single injection of the klotho gene can reduce hypertension for at least 12 weeks and possibly longer. Klotho is also available as a protein and, conceivably, we could ingest it as a powder much like we do with protein drinks," said Sun, M.D., Ph.D., a cardiovascular expert at the OU College of Medicine.
Scientists have been working with the klotho gene and its link to aging since 1997 when it was discovered by Japanese scientists. This is the first study showing that a decline in klotho protein level may be involved in the progression of hypertension and kidney damage, Sun said. With age, the klotho level decreases while the prevalence of hypertension increases.
Researchers used one injection of the klotho gene in hypertensive research models and were able to markedly reduce blood pressure by the second week. It continued to decline steadily for the length of the project - 12 weeks. The klotho gene was delivered with a safe viral vector that is currently used for gene therapy. The virus is already approved by the U.S. Food and Drug Administration for use in humans.
Researchers are studying the gene's effect for longer periods to test its ability to return blood pressure levels to normal. They also are looking at whether klotho can prevent hypertension.
http://www.scien5.com/?action-viewnews-itemid-3289 Zhongjie Sun
china？ 原文
Wang Y, Sun Z. Klotho Gene Delivery Prevents the Progression of Spontaneous Hypertension and Renal Damage.Hypertension. 2009 Jul 27. [Epub ahead of print]
Klotho is a recently discovered antiaging gene. The objective of this study was to test the hypothesis that klotho gene delivery attenuates the progression of spontaneous hypertension and renal damage in spontaneous hypertensive rats (SHRs). An adeno-associated virus (AAV) carrying mouse klotho full-length cDNA (AAV.mKL) was constructed for in vivo expression of klotho. Four groups of male SHRs and 1 group of sex- and age-matched Wistar-Kyoto rats (5 rats per group) were used. Blood pressure was measured twice in all of the animals before gene delivery. Four groups of SHRs received an IV injection of AAV.mKL, AAV.LacZ, AAV.GFP, and PBS, respectively. The Wistar-Kyoto group received PBS and served as a control. AAV.mKL stopped the further increase in blood pressure in SHRs, whereas blood pressures continued to increase in other SHR groups. One single dose of AAV.mKL prevented the progression of spontaneous hypertension for at least 12 weeks (length of the study). Klotho expression and production were suppressed in SHRs, which were reverted by AAV.mKL. AAV.mKL increased plasma interleukin 10 levels but decreased Nox2 expression, NADPH oxidase activity, and superoxide production in kidneys and aortas in SHRs. AAV.mKL abolished renal tubular atrophy and dilation, tubular deposition of proteinaceous material, glomerular collapse, and collagen deposition seen in SHRs, indicating that klotho gene delivery attenuated renal damage. Therefore, the suppressed klotho expression may play a role in the progression of spontaneous hypertension and renal damage in SHRs. AAV delivery of klotho may offer a new approach for the long-term control of hypertension and for renoprotection.
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作者:admin@医学,生命科学 2010-10-30 17:11
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