Regulation of vascular smooth muscle cell expression and function of matrix metalloproteinases is mediated by estrogen and progesterone exposure

Grandas, Oscar H.; Mountain, Deidra J.H.; Kirkpatrick, Stacy S.; Cassada, David C.; Stevens, Scott L.; Freeman, Michael B.; Goldman, Mitchell H.

doi:10.1016/j.jvs.2008.07.080

Cited by 49 publications

(42 citation statements)

References 32 publications

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“…The reasons for this gender difference are not clear, and several factors have been proposed as possible causes of this phenomenon. Hormones may be an important factor, and MMPs have been found to be targets under hormonal control in previous studies [26,27] . MMP gene expression could be regulated by hormones [28] , which are quite different between men and women.…”

Section: Discussionmentioning

confidence: 97%

Association of the polymorphisms of MMP-9 and TIMP-3 genes with thoracic aortic dissection in Chinese Han population

et al. 2014

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Aim: Thoracic aortic dissection (TAD) is the most common life-threatening disorder, and a shifted balance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is involved in TAD pathogenesis. The aim of this study was to evaluate the association of 4 single-nucleotide polymorphisms (SNPs) in MMP-9 and TIMP-3 genes with TAD risk in Chinese Han population. Methods: A total of 206 Chinese patients with TAD and 180 controls were included in this study. Four SNPs (rs3918249, rs2274756, rs9609643 and rs8136803) were genotyped using high-throughput MALDI-TOF mass spectrometry. Allele and genotype association analyses were conducted using PLINK. Results: All the 4 SNPs resulted in Hardy-Weinberg equilibrium in patients and controls. The G allele frequency for the MMP-9 SNP rs2274756 was significantly higher in female TAD patients than in female controls (P=0.0099). Moreover, after adjusting for traditional cardiovascular risk factors (sex, age, hypertension, dyslipidemia, diabetes and smoking habit), the rs2274756 polymorphism (odds ratio: 0.30; 95% confidence interval: 0.11 to 0.79, P=0.015) resulted in an independent susceptibility factor for TAD in females. No associations were found between the other SNPs and TAD. Conclusion: The results provide strong evidence for an association between MMP-9 SNP rs2274756 and female TAD risk in Chinese Han population.

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Section: Discussionmentioning

confidence: 97%

Association of the polymorphisms of MMP-9 and TIMP-3 genes with thoracic aortic dissection in Chinese Han population

et al. 2014

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“…Endocrine changes, particularly the elevations in relaxin and estrogen characteristic of mammalian pregnancy, may exert a synergistic effect, as both hormones have been implicated in MMP regulation and activation in the pregnant state (30,35). Further, MMP activation is essential in blood-flow-mediated vascular enlargement, potentially through an estrogen-mediated mechanism where increased estrogen increases MT1-MMP and MMP-2 expression (20,35,63).…”

Section: Discussionmentioning

confidence: 99%

Reduced NO signaling during pregnancy attenuates outward uterine artery remodeling by altering MMP expression and collagen and elastin deposition

Hale

Weger

Mandalà

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Hale SA, Weger L, Mandala M, Osol G. Reduced NO signaling during pregnancy attenuates outward uterine artery remodeling by altering MMP expression and collagen and elastin deposition. Am J Physiol Heart Circ Physiol 301: H1266 -H1275, 2011. First published August 19, 2011 doi:10.1152/ajpheart.00519.2011.-Recent findings indicate that endothelial nitric oxide (NO) plays a key role in uterine artery outward circumferential remodeling during pregnancy. Although the underlying mechanisms are not known, they likely involve matrix metalloproteinases (MMPs). The goal of this study was to examine the linkage among NO inhibition, expansive remodeling, and MMP expression within the uterine vascular wall. Adult female rats were treated with N G -nitro-L-arginine methyl ester [L-NAME (LPLN)] beginning on day 10 of pregnancy and until death at day 20 and compared with age-matched controls [late pregnant (LP)]. Mean arterial pressure of LPLN rats was significantly higher than controls. LPLN fetal and placental weights were significantly reduced compared with controls. Main uterine arteries (mUA) were collected to determine dimensional properties (lumen area and wall thickness), collagen and elastin content, and levels of endothelial nitric oxide synthase (eNOS) and MMP expression. Circumferential remodeling was attenuated, as evidenced by significantly smaller lumen diameters. eNOS RNA and protein were significantly (Ͼ90%) decreased in the LPLN mUA compared with LP. Collagen and elastin contents were significantly increased in LPLN rats by ϳ10 and 25%, respectively, compared with LP (P Ͻ 0.05). Both MMP-2 and tissue inhibitors of metalloproteinase-2 as assessed by immunofluorescence were lower in the endothelium (reduction of 60%) and adventitia (reduction of 50%) of LPLN compared with LP mUA. Membrane bound MMP-1 (MT1-MMP) as assessed by immunoblot was significantly decreased in LPLN. These data suggest a novel contribution of MMPs to gestational uterine vascular remodeling and substantiate the linkage between NO signaling and gestational remodeling of the uterine circulation via altered MMP, TIMP-2, and MT1-MMP expression and activity. matrix metalloproteinase; extracellular matrix; hypertension; pregnancy; nitric oxide DURING PREGNANCY, THE UTERINE vasculature undergoes significant expansive remodeling to accommodate the dramatic increase in uteroplacental blood flow that is requisite for normal pregnancy outcome. Studies from our and other laboratories (40,41,44,46,50,61) have established that nitric oxide (NO) is a key molecule involved in vascular remodeling during pregnancy and that expression of endothelial nitric oxide synthase (eNOS) is increased during pregnancy, leading to increased synthesis and release of NO from the endothelium.The importance of NO and NO signaling during pregnancy is underscored by the vascular and reproductive implications evident in mouse knockouts for endothelial NO synthase and in rats treated with the NO inhibitor N G -nitro-L-arginine methyl ester (L-NAME) during pregnancy (50, 64). Tre...

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“…Their study attributed the attenuation of IH to cell cycle arrest of VSMCs and the resulting inhibition of VSMC proliferation. Our group has previously demonstrated a direct association with the female sex hormones estrogen and progesterone on MMP-modulated ECM degradation, VSMC migration, and IH [10,12,13]. In the present study, we investigated the role of testosterone in the modulation of MMP regulatory mechanisms we have shown to be hormonally responsive and examined the influence of testosterone levels on the cellular processes of IH development.…”

Section: Introductionmentioning

confidence: 90%

Androgens regulate MMPs and the cellular processes of intimal hyperplasia

Mountain

Freeman

Kirkpatrick

et al. 2013

Journal of Surgical Research

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Regulation of vascular smooth muscle cell expression and function of matrix metalloproteinases is mediated by estrogen and progesterone exposure

Cited by 49 publications

References 32 publications

Association of the polymorphisms of MMP-9 and TIMP-3 genes with thoracic aortic dissection in Chinese Han population

Association of the polymorphisms of MMP-9 and TIMP-3 genes with thoracic aortic dissection in Chinese Han population

Reduced NO signaling during pregnancy attenuates outward uterine artery remodeling by altering MMP expression and collagen and elastin deposition

Androgens regulate MMPs and the cellular processes of intimal hyperplasia

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