Matrix Metalloproteinase Inhibition During the Development of Congestive Heart Failure

Spinale, Francis G.; Coker, Mytsi L.; Krombach, Stephen R.; Mukherjee, Rupak; Hallak, Hussein; Houck, Ward V.; Clair, Mark J.; Kribbs, Scott B.; Johnson, Linda L.; Peterson, Janet T.; Zile, Michael R.

doi:10.1161/01.res.85.4.364

Cited by 306 publications

(216 citation statements)

References 69 publications

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“…18 Thus, one mechanism by which BK exerts its protective effect on myocardial contractile function may be related to its effects on LV diastolic function. In agreement with previous reports, 15,16 this study showed a rightward shift of LV diastolic pressure-diameter curve, with an unchanged LV chamber stiffness after 3 weeks of pacing in vehicle-treated dogs. Chronic BK treatment reduced the rightward shift of the LV diastolic pressure-diameter relation but did not change LV chamber stiffness, which is in agreement with a recently developed concept.…”

Section: Tonduangu Et Al Chronic Effects Of Bradykinin In Heart Failuresupporting

confidence: 93%

“…The time constant of isovolumic LVP decay () was calculated using LVPϭP 0 e Ϫt/ , where P 0 is LVP at the start of decay and t is time. LV chamber stiffness coefficient (K) was calculated by fitting simultaneous paired LV pressure-diameter data derived from the diastolic portion of 8 successive beats to the monoexponential curve with a zero asymptote 16 (LVPϭAe kD ) and with a variable asymptote 15 (LVPϭAe kD ϩB), where A is a curve-fitting constant, D is LV diameter, and B is the pressure intercept). LV end-diastolic (ED) wall stress (g/cm 2 ) was calculated according to a simplified cylindrical model (LV long axis being not measured) as 1.36 LVEDPϫLVEDD/2 LVED wall thickness, where LVEDP is LVED pressure and LVEDD is LVED diameter.…”

Section: Data Collection and Statistical Analysismentioning

confidence: 99%

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Chronic Infusion of Bradykinin Delays the Progression of Heart Failure and Preserves Vascular Endothelium-Mediated Vasodilation in Conscious Dogs

et al. 2004

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Background-This study examined the effects of chronic bradykinin infusion on hemodynamics and myocardial and endothelial functions during the development of heart failure. Methods and Results-Sixteen instrumented dogs were randomized to receive through the left atria either vehicle or bradykinin (1 g/min) during ventricular pacing (250 bpm, 5 weeks). Hemodynamic and left ventricular (LV) parameters and the vasodilator responses to intravenous acetylcholine (0.3 to 3 g/kg) and nitroglycerin (1 to 10 g/kg) were examined in the control and after 3 and 5 weeks of pacing. The expression of endothelial NOS in femoral, carotid, and renal arteries was determined by Western blot analysis. After 3 weeks of pacing, changes in LV diastolic and systolic parameters were significantly lower in bradykinin-treated than vehicle-treated dogs (LV end-diastolic pressure, ϩ10Ϯ3 versus ϩ19Ϯ2 mm Hg; time constant of LV isovolumic relaxation, ϩ11Ϯ2 versus ϩ17Ϯ1 ms; LV wall thickening, Ϫ33Ϯ18% versus Ϫ75Ϯ9%; and cardiac output, Ϫ16Ϯ6% versus Ϫ32Ϯ6%; all PϽ0.05). Compared with vehicle-treated dogs, bradykinin-treated dogs had a reduced rightward shift of the diastolic LV pressure-diameter relation and a reduced diastolic LV wall stress. Similar trends were observed after 5 weeks. The vasodilator response to nitroglycerin was preserved in both groups. The response to acetylcholine was blunted in vehicle-treated but preserved in bradykinin-treated dogs. Vascular endothelial NOS expression decreased in vehicle-treated but was preserved in bradykinin-treated dogs. Conclusions-In

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Section: Tonduangu Et Al Chronic Effects Of Bradykinin In Heart Failuresupporting

confidence: 93%

Section: Data Collection and Statistical Analysismentioning

confidence: 99%

Chronic Infusion of Bradykinin Delays the Progression of Heart Failure and Preserves Vascular Endothelium-Mediated Vasodilation in Conscious Dogs

et al. 2004

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“…The MMP-inhibitory profile of PD166793 is shown in Table 1. Unlike first-generation MMP inhibitors, the peptide hydroxymates (eg, batimastat, marimastat), 6 PD166793 is a selective MMP inhibitor and does not inhibit other metalloproteases like tumor necrosis factor-␣ convertase.…”

Section: Mmp Inhibitor Pd166793: Specificity and Pharmacologymentioning

confidence: 99%

Matrix Metalloproteinase Inhibition Attenuates Left Ventricular Remodeling and Dysfunction in a Rat Model of Progressive Heart Failure

Peterson

Hallak²,

Johnson³

et al. 2001

Circulation

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277

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Background-Matrix metalloproteinase (MMP) activation contributes to tissue remodeling in several disease states, and increased MMP activity has been observed in left ventricular (LV) failure. The present study tested the hypothesis that MMP inhibition would influence LV remodeling and function in developing LV failure. Methods and Results-LV size and function were measured in 5 groups of rats: (1) obese male spontaneously hypertensive heart failure rats (SHHF) at 9 months (nϭ10), (2) SHHF at 13 months (nϭ12), (3) SHHF rats treated with an MMP inhibitor during months 9 to 13 (PD166793 5 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 PO; nϭ14), (4) normotensive Wistar-Furth rats (WF) at 9 months (nϭ12), and (5) WF at 13 months (nϭ12). Plasma concentrations of the MMP inhibitor (116Ϯ11 mol/L) reduced in vitro LV myocardial MMP-2 activity by Ϸ100%. LV function and geometry were similar in WF rats at 9 and 13 months. LV peak ϩdP/dt was unchanged at 9 months in SHHF but by 13 months was reduced in the SHHF group compared with WF (3578Ϯ477 versus 5983Ϯ109 mm Hg/s, PՅ0.05). LV volume measured at an equivalent ex vivo pressure (10 mm Hg) was increased in SHHF at 9 months compared with WF (443Ϯ12 versus 563Ϯ33 mL, PՅ0.05) and increased further by 13 months (899Ϯ64 mL, PՅ0.05). LV myocardial MMP-2 activity was increased by Ϸ2-fold in SHHF at 9 and 13 months. With MMP inhibition, LV peak ϩdP/dt was similar to WF values and LV volume was reduced compared with untreated SHHF values (678Ϯ28 mL, PՅ0.05). Conclusions-MMP

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“…4 -8 The previous studies assessed the expression and activity of MMPs after LV dilatation occurred, and preventive pharmacological inhibition of MMPs resulted in incomplete suppression of LV remodeling in animal HF models. 9,10 There is no doubt about the crucial roles of MMPs in promoting LV remodeling; however, it remains unclear whether activation of MMPs precedes or follows LV dilatation. Previous in vitro studies showed that ACE inhibition attenuated MMP activity, 7,11 and long-term ACE inhibition decreased MMP activity with attenuation of LV dilatation in animal studies.…”

mentioning

confidence: 99%

Activation of Matrix Metalloproteinases Precedes Left Ventricular Remodeling in Hypertensive Heart Failure Rats

et al. 2004

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Background-Matrix metalloproteinases (MMPs) are activated in dilated failing hearts, and angiotensin-converting enzyme (ACE) inhibition prevents left ventricular (LV) dilatation. However, it remains unclear whether activation of MMPs precedes or is secondary to LV remodeling, and an effect of ACE inhibition on MMPs is unknown. Methods and Results-Dahl salt-sensitive rats fed a high-salt diet from 8 weeks served as the hypertensive heart failure (HF) model. LV echo, histological study, measurement of mRNA levels, and gelatin zymography were performed before (at 23 weeks) and after (at 26 weeks) the development of LV dilatation and pulmonary edema. The same procedures were conducted in the HF model rats treated with a subdepressor dose of ACE inhibitor (enalapril 5 mg · kg Ϫ1 · d

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Matrix Metalloproteinase Inhibition During the Development of Congestive Heart Failure

Cited by 306 publications

References 69 publications

Chronic Infusion of Bradykinin Delays the Progression of Heart Failure and Preserves Vascular Endothelium-Mediated Vasodilation in Conscious Dogs

Chronic Infusion of Bradykinin Delays the Progression of Heart Failure and Preserves Vascular Endothelium-Mediated Vasodilation in Conscious Dogs

Matrix Metalloproteinase Inhibition Attenuates Left Ventricular Remodeling and Dysfunction in a Rat Model of Progressive Heart Failure

Activation of Matrix Metalloproteinases Precedes Left Ventricular Remodeling in Hypertensive Heart Failure Rats

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