Contribution of Plasma Matrix Metalloproteinases to Development of Left Ventricular Hypertrophy and Diastolic Dysfunction in Hypertensive Subjects

Sağlam, Mustafa; Karakaya, Osman; Esen, Ali Metin; Barutçu, İrfan; Doğan, Serkan; Karaveli̇oğlu, Yusuf; Karapınar, Hekim; Akgün, Taylan; Esen, Özlem; Özdemir, Nihal; Türkmen, Sembol; Kaymaz, Ci̇hangi̇r

doi:10.1620/tjem.208.117

Cited by 23 publications

(21 citation statements)

References 18 publications

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“…These results contrast with studies in noninfectious settings, in which MMP-9 has been associated with maladaptive remodeling in both animal models and humans: MMP-9 levels are increased in the plasma of patients presenting with hypertension-induced hypertrophy 26 or congestive heart failure 27 and after ischemic attacks, 28 -30 which correlates with decreased cardiac function and adverse structural alterations. In light of these studies, it is apparent that MMP-9 plays a key role in innate immunity and clearance of cardiac infection, but it is also associated with cardiac injury.…”

Section: Discussioncontrasting

confidence: 82%

Ablation of Matrix Metalloproteinase-9 Increases Severity of Viral Myocarditis in Mice

et al. 2008

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Background-Coxsackievirus B3 (CVB3) causes human myocarditis, which can result in cardiac damage, maladaptive remodeling, and heart failure. Matrix metalloproteinases (MMP)-8 and -9 have been identified in virus-infected myocardium, but their particular roles and underlying mechanisms of effect are unknown. For the first time, we examine the severity of CVB3-induced myocarditis in MMP-8 -and MMP-9 -deficient mice. Methods and Results-CVB3-infected MMP-8 and MMP-9 knockout (KO) mice and corresponding wild-type (WT) mice were euthanized and harvested at 9 days after infection. Expression of MMP-2, -8, -12, and -13 and tissue inhibitors of MMPs was assessed by zymography or immunoblotting on harvested hearts, and in situ hybridization was performed to detect active infection. Infected MMP-9 KO mice had greater myocardial injury and foci of infection than WT mice despite similar pancreatic infection. Increased fibrosis (10.6Ϯ2.7% versus 7.1Ϯ2.6%, Pϭ0.04), viral titer, as well as decreased cardiac output, were evident in MMP-9 KO compared with WT mice as assessed by picrosirius red staining, plaque assay, and echocardiography, respectively. Immune infiltration was also greatly increased in MMP-9 KO compared with WT mice (15.2Ϯ12.6% versus 2.0Ϯ3.0%, PϽ0.002). Myocardial interferon-␤1, interferon-␥, interleukin-6, interleukin-10, and macrophage inflammatory protein-1␣ expression was elevated in MMP-9 KO mice as measured by quantitative real-time polymerase chain reaction and ELISA. In contrast, MMP-8 KO mice had the same degree of cardiac injury, fibrosis, and viral infection as their WT counterparts. Conclusions-During acute CVB3 infection, MMP-9 appears necessary to halt virus propagation in the heart, promote proper immune infiltration and remodeling, and preserve cardiac output.

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Section: Discussioncontrasting

confidence: 82%

Ablation of Matrix Metalloproteinase-9 Increases Severity of Viral Myocarditis in Mice

et al. 2008

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“…Although not directly indicated in these studies, one can speculate that some of the MMP-2 induction occurs within the vascular endothelium; however, this requires more definitive investigation. Furthermore, other studies have demonstrated that cyclic strain-induced endothelial MMP-9 contributes to hypertensive remodeling in rats and humans (126).…”

Section: Cyclic Strain and Endothelial Dysfunction: Relevance To Vascmentioning

confidence: 98%

Cyclic strain-mediated matrix metalloproteinase regulation within the vascular endothelium: a force to be reckoned with

Cummins¹,

Sweeney²,

Killeen³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Cummins PM, von Offenberg Sweeney N, Killeen MT, Birney YA, Redmond EM, Cahill PA. Cyclic strain-mediated matrix metalloproteinase regulation within the vascular endothelium: a force to be reckoned with. Am J Physiol Heart Circ Physiol 292: H28 -H42, 2007. First published September 1, 2006; doi:10.1152/ajpheart.00304.2006.-The vascular endothelium is a dynamic cellular interface between the vessel wall and the bloodstream, where it regulates the physiological effects of humoral and biomechanical stimuli on vessel tone and remodeling. With respect to the latter hemodynamic stimulus, the endothelium is chronically exposed to mechanical forces in the form of cyclic circumferential strain, resulting from the pulsatile nature of blood flow, and shear stress. Both forces can profoundly modulate endothelial cell (EC) metabolism and function and, under normal physiological conditions, impart an atheroprotective effect that disfavors pathological remodeling of the vessel wall. Moreover, disruption of normal hemodynamic loading can be either causative of or contributory to vascular diseases such as atherosclerosis. EC-matrix interactions are a critical determinant of how the vascular endothelium responds to these forces and unquestionably utilizes matrix metalloproteinases (MMPs), enzymes capable of degrading basement membrane and interstitial matrix molecules, to facilitate force-mediated changes in vascular cell fate. In view of the growing importance of blood flow patterns and mechanotransduction to vascular health and pathophysiology, and considering the potential value of MMPs as therapeutic targets, a timely review of our collective understanding of MMP mechanoregulation and its impact on the vascular endothelium is warranted. More specifically, this review primarily summarizes our current knowledge of how cyclic strain regulates MMP expression and activation within the vascular endothelium and subsequently endeavors to address the direct and indirect consequences of this on vascular EC fate. Possible relevance of these phenomena to vascular endothelial dysfunction and pathological remodeling are also addressed. endothelial cells; smooth muscle; shear stress MECHANICAL OR HEMODYNAMIC forces associated with blood flow play a pivotal role in the physiological control of vascular tone, remodeling, and the initiation and progression of vascular pathologies. Disruption of normal hemodynamic loading can be either causative of or contributory to several life-threatening diseases including hypertension (HT), intimal hyperplasia (IH), and atherosclerosis. With respect to the latter, for example, a variety of systemic risk factors (e.g., smoking, hyperlipidemia, genetic factors) have been found to promote atherosclerosis. Although these factors affect blood vessels equally, atherosclerotic lesions typically develop at predictable locations (e.g., branch points, bifurcations, sites of injury and infection), suggesting that the development of clinically significant plaques involves a complex interplay between vascular anatomy,...

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“…Med., a study by Saglam et al (2006) adds further weight to the hypothesis that plasma MMPs play a role in the development of LVH and diastolic dysfunction in hypertensive subjects. Their study group included 27 hypertensive patients with LVH and 23 without LVH; they found that plasma MMP-3 and Sundstrom et al (2004) TIMP-1 1069 Plasma TIMP-1 was positively associated with LV mass, wall thickness, relative wall thickness, end-systolic diameter, and LA diameter, increased LVEDD or wall thickness, and negatively correlated with fractional shortening.…”

mentioning

confidence: 99%

“…One previous study (Li-Saw-Hee et al 2000) explored the potential effects of treating hypertensive patients with an ACE-inhibitor or an ARB, albeit for a short period of time (about 2 months) and found no significant alteration in the MMP-9 and TIMP-1 levels, despite a fall in blood pressure (average treated blood pressure 143/85 mmHg). A follow up of the patients with LVH in the study by Saglam et al (2006), after treatment with an ACE-inhibitor or an ARB to assess for LVH regression as well as a fall in the MMP levels, that can be linked to a change in indices of diastolic dysfunction, would be interesting. Certainly, other short term treatment studies (Zervoudaki et al 2003) suggest that this may potentially be the case.…”

mentioning

confidence: 99%

“…Certainly, other short term treatment studies (Zervoudaki et al 2003) suggest that this may potentially be the case. Also, the present study by Saglam et al (2006) was limited to assays of only 2 out of the over 20 members of MMPs, with no corresponding assay of their inhibitor, TIMP-1. TIMP-1, as discussed above, has been shown in 4 out of the 7 studies to be related to LV mass, mass index and parameters of diastolic dysfunction ( Table 2).…”

mentioning

confidence: 99%

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Matrix Metalloproteinases and Hypertension: A Link between Left Ventricular Hypertrophy and Diastolic Dysfunction?

Karthikeyan

Lip

2006

Tohoku J. Exp. Med.

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Contribution of Plasma Matrix Metalloproteinases to Development of Left Ventricular Hypertrophy and Diastolic Dysfunction in Hypertensive Subjects

Cited by 23 publications

References 18 publications

Ablation of Matrix Metalloproteinase-9 Increases Severity of Viral Myocarditis in Mice

Ablation of Matrix Metalloproteinase-9 Increases Severity of Viral Myocarditis in Mice

Cyclic strain-mediated matrix metalloproteinase regulation within the vascular endothelium: a force to be reckoned with

Matrix Metalloproteinases and Hypertension: A Link between Left Ventricular Hypertrophy and Diastolic Dysfunction?

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