Hypertension, matrix metalloproteinases and target organ damage

Donnelly, Richard; Collinson, Deborah J; Manning, Gillian

doi:10.1097/00004872-200309000-00009

Cited by 26 publications

(26 citation statements)

References 29 publications

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“…Moreover, increased MMP-2 levels may contribute to vascular dysfunction (Castro et al, 2008(Castro et al, , 2010 secondary to hypertension-related mechanical stress on the vascular wall (Donnelly et al, 2003). Therefore, although we have not assessed vascular MMP-2 levels in the present study, the higher MMP-2/TIMP-2 ratios that we found in gestational hypertension may well reflect these mechanisms.…”

Section: Discussionmentioning

confidence: 71%

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

Palei

Sandrim

Amaral

et al. 2012

Experimental and Molecular Pathology

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Section: Discussionmentioning

confidence: 71%

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

Palei

Sandrim

Amaral

et al. 2012

Experimental and Molecular Pathology

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“…A recent study by Brassard et al (2005) underlines this view assuming that the beneficial effects of AT 2 receptors are in part due to increases of elastin deposition and are attributable to a decline in MMP-2 activity. In this context, it is important to note that MMP-2 and MMP-9 are particularly efficient in degrading collagen IV-the major structural component of the physiologic mesangial matrix and glomerular basement membrane-and elastin (Lenz et al, 2000;Donnelly et al, 2003), whereas collagen III is degraded by interstitial collagenases. Thus, assuming the up-regulation of MMP-2 as a reaction to and not a cause of fibrosis the increase would not help to counteract the increase of collagen III.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to membrane-bound membranetype MMPs, MMPs such as MMP-2 and MMP-9 are secreted in an inactive form and are subsequently activated extracellularly by other already activated MMPs or serine proteinases (Sternlicht and Werb, 2001;Snoek-van Beurden and Von den Hoff, 2005). In the kidney, MMP-2 and -9 are expressed in the glomerulus, and several reports indicate their importance in controlling ECM turnover in disease states (Lenz et al, 2000;Lelongt et al, 2001;Donnelly et al, 2003). Regulation of MMP activity is controlled at three levels: transcription, activation of the proenzyme, and inhibition by TIMPs.…”

mentioning

confidence: 99%

“…Regulation of MMP activity is controlled at three levels: transcription, activation of the proenzyme, and inhibition by TIMPs. Four TIMPs, i.e., TIMP1-4, have been described in vertebrates so far, among which TIMP-1 and -2 are expressed in glomeruli (Donnelly et al, 2003). Changes of TIMP levels are considered to be important because they directly affect the levels of MMP activity since they have the ability to form tight 1:1 complexes with the active MMP enzymes (Sternlicht and Werb, 2001).…”

mentioning

confidence: 99%

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Expression and Response to Angiotensin-Converting Enzyme Inhibition of Matrix Metalloproteinases 2 and 9 in Renal Glomerular Damage in Young Transgenic Rats with Renin-Dependent Hypertension

Bolbrinker

Marković²,

Wehland³

et al. 2005

J Pharmacol Exp Ther

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Extracellular matrix expansion in the glomerular mesangium contributes to the development of glomerulosclerosis and chronic renal disease in arterial hypertension. Transforming growth factor-␤1 (TGF-␤1), matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) are involved in this process. Conflicting data are reported on the effects of angiotensin II (Ang II) and the response to angiotensin-converting enzyme inhibition on MMPs and TIMPs in early stages of hypertensive glomerular damage. We therefore investigated the effects of Ang II-dependent hypertension on MMP-2, MMP-9, TIMP-1, and TIMP-2 in isolated glomeruli of 8-week-old homozygous male rats overexpressing the mouse Ren2 gene [TGR(mRen2)27]. At this age, systolic blood pressure was already significantly elevated in Ren2 compared with SpragueDawley (SD) rats (197 Ϯ 38 versus 125 Ϯ 16 mm Hg, p Ͻ 0.01). Ren2 exhibited renal damage as determined by increased urinary albumin excretion, focal glomerulosclerosis, mesangial matrix expansion, and ␣-smooth muscle actin deposition. Quantification of mRNA levels in isolated glomeruli by real-time polymerase chain reaction showed a significant increase of TGF-␤1, a 2.3-and a 2.6-fold increase of MMP-2 and TIMP-1 in Ren2 compared with SD (p Ͻ 0.01, respectively) and no strain differences for TIMP-2. In contrast, MMP-9 mRNA expression was markedly suppressed to 10% of control levels in Ren2 (p Ͻ 0.01). Early treatment with ramipril completely prevented renal damage in Ren2 and restored mRNA expression of TGF-␤1, MMP-2, and TIMP-1 to SD control levels. Interestingly, down-regulation of MMP-9 mRNA, protein, and activity was not affected by ramipril, indicating that the protective effect of this compound is not attributable to restoration of MMP-9 in the glomerulus.

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“…29 However, because TIMP-1 is an important endogenous MMP-9 inhibitor, the increased TIMP-1 levels found in both PE and GH has led to similar MMP-9/TIMP-1 ratios in PE and GH compared with HP, thus suggesting that similar net MMP-9 activity exist in patients with hypertensive disorders of pregnancy as compared with HP.…”

Section: Act Palei Et Almentioning

confidence: 99%

Matrix metalloproteinase-9 polymorphisms affect plasma MMP-9 levels and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

et al. 2011

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Abnormal matrix metalloproteinase (MMP)-9 levels may have a role in hypertensive disorders of pregnancy. We examined whether MMP-9 genetic polymorphisms (g.À1562C4T and g.À90(CA) 13À25 ) modify plasma MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels and the responses to antihypertensive therapy in 214 patients with preeclampsia (PE), 185 patients with gestational hypertension (GH) and a control group of 214 healthy pregnant (HP). Alleles for the g.À90(CA) 13À25 polymorphism were grouped L (low) (o21 CA repeats) or H (high) (X21 CA repeats). Plasma MMP-9 and TIMP-1 concentrations were measured by enzyme-linked immunosorbent assay. Plasma MMP-9 concentrations were not affected by genotypes or haplotypes in HP and PE groups, except for the g.À90(CA) 13À25 polymorphism: GH patients with the LH genotype for this polymorphism have higher MMP-9 levels than those with other genotypes. The T allele for the g.À1562C4T polymorphism and the H4 haplotype (combining T and H alleles) are associated with GH and lack of responsiveness to antihypertensive therapy in GH. The H2 haplotype (combining C and H alleles) was associated with lack of responsiveness to antihypertensive therapy in PE, but not in GH. In conclusion, our results show that MMP-9 genetic variants are associated with GH and suggest that MMP-9 haplotypes affect the responsiveness to antihypertensive therapy in hypertensive disorders of pregnancy.

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Hypertension, matrix metalloproteinases and target organ damage

Cited by 26 publications

References 29 publications

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

Expression and Response to Angiotensin-Converting Enzyme Inhibition of Matrix Metalloproteinases 2 and 9 in Renal Glomerular Damage in Young Transgenic Rats with Renin-Dependent Hypertension

Matrix metalloproteinase-9 polymorphisms affect plasma MMP-9 levels and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

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