JOURNAL ARTICLE

Angiotensin II, transforming growth factor-beta1 and repair in the infarcted heart

Y Sun, J Q Zhang, J Zhang, F J Ramires
Journal of Molecular and Cellular Cardiology 1998, 30 (8): 1559-69
9737942
Tissue repair following myocardial infarction (MI) eventuates in fibrous tissue formation at the site of myocyte necrosis. Following a large transmural MI, fibrosis appears remote to the infarct site. This is associated with extensive tissue remodeling that adversely affects ventricular diastolic function. Substances involved in promoting fibrous tissue formation at MI and remote sites are under investigation. Angiotensin II (AngII), generated at sites of repair, has been implicated. However, its regulatory role on fibrous tissue formation remains uncertain. In the present study we sought to determine whether AngII is correlated to transforming growth factor beta 1 (TGF-beta1) expression, a regulator of fibrous tissue formation, at these sites of tissue repair. We studied: (1) localization and expression of angiotensin converting enzyme (ACE), AngII receptors, TGF-beta1 mRNA and its receptors in the infarcted rat heart; and (2) effect of AngII on TGF-beta1 synthesis by chronic blockade of AT1 receptors began at the time of surgery by losartan in rats with MI. Hearts were studied at 4 weeks post-MI. We found: (1) low-density ACE, AngII and TGF-beta1 receptor binding and low mRNA for type I collagen and TGF-beta1 in the normal heart; (2) fibrosis at sites of MI and remote to it, including endocardium and fibrosis of intraventricular septum, interstitial fibrosis of non-infarcted myocardium and fibrosis of visceral pericardium; (3) markedly increased (P<0.01) and colocalized ACE, AngII and TGF-beta1 receptor binding, type I collagen and TGF-beta1 mRNA at MI and remote sites of repair; (4) increased TGF-beta1 concentration (P<0. 01) at these sites; and (5) attenuated TGF-beta1 and type I collagen gene expression (P<0.01) at these sites in rats receiving losartan. These observations suggest locally generated AngII via ATi receptor binding is correlated to TGF-beta1 expression and synthesis at sites of repair and remote sites in the infarcted rat heart. The mechanism responsible for the role of AngII in TGF-beta1 remains to be elucidated.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
9737942
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"