Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dilatation in patients with asymptomatic systolic dysfunction. SOLVD (Studies of Left Ventricular Dysfunction) Investigators.

Konstam, Marvin A.; Kronenberg, Marvin W.; Rousseau, Michel F.; Udelson, James E.; Melin, Jacques; Stewart, Duncan J.; Dolan, Noreen; Edens, Tonya R.; Ahn, Sylvie A.; Kinan, Debra

doi:10.1161/01.cir.88.5.2277

Cited by 282 publications

(144 citation statements)

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“…Second, direct pharmacological MMP inhibition in this chronic rapid pacing model reduced the degree of LV dilation but did not influence intrinsic contractile function (30). Third, the relative changes in LV volumes with developing heart failure appear to be independent of ejection performance as it relates to clinical outcomes (3,16). In the present study, LV ejection fraction was unchanged in the TNF-␣ blocking group but end-diastolic volume was reduced, implying that intrinsic myocardial contractility may have been altered.…”

Section: Discussionmentioning

confidence: 50%

“…Myocardial remodeling can be defined as structural changes in the cellular and extracellular matrix resulting in compositional changes within the LV wall. An acceleration of the LV remodeling process is associated with greater morbidity and mortality in patients with LV failure (3,16). While a number of biological systems influence myocardial matrix structure and function, a family of proteases called matrix metalloproteinases (MMPs) likely contributes to the remodeling process (4, 8, 12-15, 18, 26, 29-31).…”

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confidence: 99%

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TNF-α and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling

Bradham

Moe

Wendt

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

113

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. TNF-␣ and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling. Am J Physiol Heart Circ Physiol 282: H1288-H1295, 2002; 10.1152/ajpheart.00526. 2001.-The cytokine tumor necrosis factor (TNF)-␣ has been causally linked to left ventricular (LV) remodeling, but the molecular basis for this effect is unknown. Matrix metalloproteinases (MMPs) have been implicated in cardiac remodeling and can be regulated by TNF-␣. This study tested the central hypothesis that administration of a TNF-␣ blocking protein would prevent the induction of MMPs and alter the course of myocardial remodeling in developing LV failure. Adult dogs were randomly assigned to the following groups: 1) chronic pacing (250 beats/min, 28 days, n ϭ 12), 2) chronic pacing with concomitant administration of a TNF-␣ blocking protein (TNF block) using a soluble p75 TNF receptor fusion protein (TNFR:Fc; administered at 0.5 mg/kg twice a week subcutaneously, n ϭ 7), and 3) normal controls (n ϭ 10). LV end-diastolic volume increased from control with chronic pacing (83 Ϯ 12 vs. 118 Ϯ 10 ml, P Ͻ 0.05) and was reduced with TNF block (97 Ϯ 9 ml, P Ͻ 0.05). MMP zymographic levels (92 kDa, pixels) increased from control with chronic pacing (36,848 Ϯ 9,593 vs. 87,247 Ϯ 12,912, P Ͻ 0.05) and was normalized by TNF block. Myocardial MMP-9 and MMP-13 levels by immunoblot increased with chronic pacing relative to controls (130 Ϯ 10% and 118 Ϯ 6%, P Ͻ 0.05) and was normalized by TNF block. These results provide evidence to suggest that TNF-␣ contributes to the myocardial remodeling process in evolving heart failure through the local induction of specific MMPs.tumor necrosis factor-␣; chronic pacing A MILESTONE IN THE DEVELOPMENT of left ventricular (LV) failure is myocardial remodeling. Myocardial remodeling can be defined as structural changes in the cellular and extracellular matrix resulting in compositional changes within the LV wall. An acceleration of the LV remodeling process is associated with greater morbidity and mortality in patients with LV failure (3, 16). While a number of biological systems influence myocardial matrix structure and function, a family of proteases called matrix metalloproteinases (MMPs) likely contributes to the remodeling process (4, 8, 12-15, 18, 26, 29-31). MMP activity is regulated at several levels, including transcription and posttranslational modification (8, 21). MMP activity can be inhibited by an endogenous class of proteins called the tissue inhibitors of MMPs (TIMPs). A number of biologically active molecules can induce MMP expression, including the pleotrophic cytokine tumor necrosis factor (TNF)-␣, which has been demonstrated to increase MMPs in vitro (10, 25). Increased TNF-␣ levels have been previously associated with LV myocardial remodeling (1, 17). TNF-␣ is synthesized as a membrane-bound protein and subsequently processed and cleaved to a soluble form that circulates as a stable homotrimer (5). TNF-␣ binding to cell surface receptors results in the activation of intracellular signaling ...

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Section: Discussionmentioning

confidence: 50%

mentioning

confidence: 99%

TNF-α and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling

Bradham

Moe

Wendt

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

113

View full text Add to dashboard Cite

show abstract

“…Studies in patients with CHF functional classes III and IV demonstrate that ACE-I have a strong impact in the life quality and long-term survival 76,77 , which allows us to conclude that these drugs must not be suspended in the decompensated phase, except in cases of hyperkalemia, marked impairment of renal function or major and refractory hypotension.…”

Section: Angiotensin-converting Enzyme Inhibitors (Ace-i) (Tables 17 mentioning

confidence: 99%

I Diretriz Latino-Americana para avaliação e conduta na insuficiência cardíaca descompensada

Bocchi¹,

Vilas-Boas²,

Perrone³

et al. 2005

Arq. Bras. Cardiol.

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“…Furthermore, we observed a significant beneficial effect of enalapril on ventricular remodeling within a substudy of SOLVD Prevention. 13 It is therefore likely that the positive survival trend observed in this trial would have reached statistical significance with a larger number of events.…”

Section: See P 249mentioning

confidence: 87%

Endothelin Expression and the Progression of Heart Failure

Konstam

DeNofrio

2004

Circulation

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Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dilatation in patients with asymptomatic systolic dysfunction. SOLVD (Studies of Left Ventricular Dysfunction) Investigators.

Abstract: Chronic ACE inhibitor treatment slows or reverses LV dilatation in patients with asymptomatic LV systolic dysfunction. Compared with symptomatic patients, asymptomatic patients manifest a slower rate of spontaneous LV dilatation and less reduction in LV volumes by enalapril.

Cited by 282 publications

References 29 publications

TNF-α and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling

TNF-α and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling

I Diretriz Latino-Americana para avaliação e conduta na insuficiência cardíaca descompensada

Endothelin Expression and the Progression of Heart Failure

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