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Plasminogen activator inhibitor-1 antagonist TM5441 ...

aging hypertensi

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#1 jans

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Posted 02 May 2014 - 11:30 AM


interesting study. Would this work for people? http://www.ncbi.nlm....pubmed/24092817

 

"Plasminogen activator inhibitor-1 antagonist TM5441 attenuates Nω-nitro-L-arginine methyl ester-induced hypertension and vascular

Abstract
BACKGROUND:

Long-term inhibition of nitric oxide synthase by L-arginine analogues such as N(ω)-nitro-l-arginine methyl ester (L-NAME) has been shown to induce senescence in vitro and systemic hypertension and arteriosclerosis in vivo. We previously reported that plasminogen activator inhibitor-1 (PAI-1)-deficient mice (PAI-1(-/-)) are protected against L-NAME-induced pathologies. In this study, we investigated whether a novel, orally active PAI-1 antagonist (TM5441) has a similar protective effect against L-NAME treatment. Additionally, we studied whether L-NAME can induce vascular senescence in vivo and investigated the role of PAI-1 in this process.

METHODS AND RESULTS:

Wild-type mice received either L-NAME or L-NAME and TM5441 for 8 weeks. Systolic blood pressure was measured every 2 weeks. We found that TM5441 attenuated the development of hypertension and cardiac hypertrophy compared with animals that had received L-NAME alone. Additionally, TM5441-treated mice had a 34% reduction in periaortic fibrosis relative to animals on L-NAME alone. Finally, we investigated the development of vascular senescence by measuring p16(Ink4a) expression and telomere length in aortic tissue. We found that L-NAME increased p16(Ink4a) expression levels and decreased telomere length, both of which were prevented with TM5441 cotreatment.

CONCLUSIONS:

Pharmacological inhibition of PAI-1 is protective against the development of hypertension, cardiac hypertrophy, and periaortic fibrosis in mice treated with L-NAME. Furthermore, PAI-1 inhibition attenuates the arterial expression of p16(Ink4a) and maintains telomere length. PAI-1 appears to play a pivotal role in vascular senescence, and these findings suggest that PAI-1 antagonists may provide a novel approach in preventing vascular aging and hypertension."

 



#2 midas

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Posted 03 May 2014 - 03:29 PM

Experimental Drug TM5441 Prolongs Life Span 4x In Mice

 

http://www.science20..._in_mice-135417



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