Targeted Deletion of Matrix Metalloproteinase 2 Ameliorates Myocardial Remodeling in Mice With Chronic Pressure Overload

Matsusaka, Hidenori; Ide, Tomomi; Matsushima, Shouji; Ikeuchi, Masaki; Kubota, Takeshi; Sunagawa, Kenji; Kinugawa, Shintaro; Tsutsui, Hiroyuki

doi:10.1161/01.hyp.0000208840.30778.00

Cited by 157 publications

(121 citation statements)

References 32 publications

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“…However, the results were inconsistent and appeared to depend on the animal model used. Chronic pressure overload in MMP-2-deficient mice is associated with reduced cardiac interstitial fibrosis and MMP-2 transgenic mice have been reported to be associated with increased replacement fibrosis and perivascular fibrosis (25,26). The results of the present study support the theory that the degenerative activity of MMP-2 is markedly impaired in the fibrotic myocardium.…”

Section: Discussionsupporting

confidence: 83%

Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in mice associated with upregulation and activation of matrix metalloproteinase-2

Yang

Kui-ying

et al. 2012

Mol Med Report

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Abstract.Cryptotanshinone is an active ingredient of Salvia miltiorrhiza that has been used in traditional Chinese medicine for treating cardiovascular disorders. Thus, we investigated the effects of cryptotanshinone on cardiac fibrosis induced by isoprenaline and examined whether cardiac matrix metalloproteinase (MMP)-2 is involved in this process. Male C57BL/6 mice received a daily injection of 0.9% saline, 3 mg/kg isoprenaline or isoprenaline plus 20 mg/kg cryptotanshinone by gastric gavage for 2 weeks. In this study we demonstrated that cryptotanshinone was able to significantly ameliorate isoprenaline-induced cardiac fibrosis, which was associated with a marked upregulation and activation of MMP-2 in the ventricular myocardium. Additionally, we demonstrated that cryptotanshinone dose-dependently upregulated and activated MMP-2 in cultured cardiac fibroblasts. Moreover, incubation with cryptotanshinone also prevented the isoprenaline-induced downregulation and inactivation of MMP-2 in cultured cardiac fibroblasts. Taken together, our data suggest that cryptotanshinone is a novel and potent antifibrotic agent. The present findings further our understanding of the role of MMP-2 in cardiac fibrosis and the antifibrotic mechanisms of cryptotanshinone.

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Section: Discussionsupporting

confidence: 83%

Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in mice associated with upregulation and activation of matrix metalloproteinase-2

Yang

Kui-ying

et al. 2012

Mol Med Report

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“…Another possible mechanism is the contribution of myocardial MMP-2 expression in this model, since it has been reported that MMP activation plays an important role in the pathophysiology of LV remodeling (27,28) and, moreover, since myocardial MMPs can be activated by Ang II (29). Based on these findings, the activation of the renin-angiotensin system might contribute to the activation of MMP-2 and thus to the development of LV remodeling in the diabetic heart.…”

Section: Discussionmentioning

confidence: 71%

Angiotensin II Type 1 Receptor Blocker Attenuates Myocardial Remodeling and Preserves Diastolic Function in Diabatic Heart

et al. 2007

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“…29 In this respect, transgenic models have contributed to the understanding of the roles for MMPs in LVH, and MMP-2 knockout mice present interesting reductions in LVH and its complications in models of heart hypertrophy. 30 These mice have increased TIMP-4 levels in the heart, and TIMP-4 is a major MMPs inhibitor. 31 Whether the reduced LVH seen in these animals is because of lack of MMP-2 activity or to the inhibitory effects of TIMP-4 on various MMPs is not known.…”

Section: Discussionmentioning

confidence: 99%

Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients

et al. 2011

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Matrix metalloproteinases (MMPs) are involved in cardiac remodelling. We examined whether MMP-2 genetic polymorphisms are associated with hypertension and left ventricular (LV) remodelling in hypertensive patients. We studied 160 hypertensive patients and 123 healthy controls. Echocardiography was performed in all patients and the C À1306 T (rs243865) and C À735 T (rs 2285053) MMP-2 polymorphisms were analysed. Haplo.stats analysis was used to evaluate whether MMP-2 haplotypes are associated with hypertension and with extremes in LV mass index (LVMI). Multiple linear regression analysis was performed to assess whether MMP-2 genotypes or haplotypes affect LVMI and other echocardiography parameters. The C À1306 T 'CC' genotype was associated with reduced LVMI and LV end-diastolic diameter (EDD) (P ¼ 0.0365 and P ¼ 0.0438, respectively). The haplotype 'C, C' was associated with reduced LVMI and EDD (P ¼ 0.0278 and P ¼ 0.0322, respectively). The comparison of upper and lower extremes of the LVMI phenotype showed that the 'C, C' haplotype was more common in the lower LVMI group (P ¼ 0.0060), whereas the 'T, C' haplotype was more common in the higher quartile of LVMI (P ¼ 0.0187), and this haplotype was associated with increased risk of higher LVMI values (odds ratio ¼ 3.5121, 95% confidence interval ¼ 1.3193-9.3494). The findings suggest that MMP-2 polymorphisms affect hypertension-induced LV remodelling.

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Targeted Deletion of Matrix Metalloproteinase 2 Ameliorates Myocardial Remodeling in Mice With Chronic Pressure Overload

Cited by 157 publications

References 32 publications

Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in mice associated with upregulation and activation of matrix metalloproteinase-2

Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in mice associated with upregulation and activation of matrix metalloproteinase-2

Angiotensin II Type 1 Receptor Blocker Attenuates Myocardial Remodeling and Preserves Diastolic Function in Diabatic Heart

Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients

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