Cause and effect relationship between myocardial mast  cell number and matrix metalloproteinase activity

Brower, Gregory L.; Chancey, Amanda L.; Thanigaraj, Srihari; Matsubara, Beatriz Bojikian; Janicki, Joseph S.

doi:10.1152/ajpheart.00218.2000

Cited by 124 publications

(174 citation statements)

References 35 publications

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“…Mast cell-mediated MMP activation, leading to degradation of the extracellular matrix and ventricular dilatation, are well-documented features in this model of heart failure (3,6,8,9,20). The stimulus initiating this mast cell-mediated remodeling is unknown; however, we recently demonstrated that ET-1 is capable of causing cardiac mast cell degranulation and the subsequent activation of MMPs ex vivo (31).…”

Section: Discussionmentioning

confidence: 80%

“…Previous work using the AV fistula model of chronic volume overload established a causal role for cardiac mast cells in the regulation of MMP activity (3,8). Mast cell-mediated MMP activation, leading to degradation of the extracellular matrix and ventricular dilatation, are well-documented features in this model of heart failure (3,6,8,9,20).…”

Section: Discussionmentioning

confidence: 85%

“…Subsequent to this, the remodeling consists of return-to-near-normal collagen values in the myocardium between 7 to 14 days. Concomitant chamber dilatation developing in this initial period rapidly stabilizes and does not progress further until beyond 4 to 5 wk postfistula (3)(4)(5).…”

Section: Experimental Designmentioning

confidence: 98%

“…Previous studies from our laboratory using the aortocaval (AV) fistula model of volume overload established a causal role for cardiac mast cells in the activation of matrix metalloproteinases (MMPs) (3,8,22,31). The role of MMPs in mediating the degradation of the extracellular matrix leading to ventricular dilatation has been well documented (3,6,9,20,38). However, the potential for ET-1 to directly impact myocardial remodeling was recently established by our study, demonstrating that ET-1 causes degranulation of resident cardiac mast cells (31).…”

mentioning

confidence: 99%

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Effects of nonselective endothelin-1 receptor antagonism on cardiac mast cell-mediated ventricular remodeling in rats

Murray

Gardner²,

Brower³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Murray DB, Gardner JD, Brower GL, Janicki JS. Effects of nonselective endothelin-1 receptor antagonism on cardiac mast cellmediated ventricular remodeling in rats. Am J Physiol Heart Circ Physiol 294: H1251-H1257, 2008. First published January 4, 2008 doi:10.1152/ajpheart.00622.2007.-The objective of this study was to investigate the effect a nonselective endothelin-1 (ET-1) receptor antagonist (bosentan) had on the acute myocardial remodeling process including left ventricular (LV) mast cells and matrix metalloproteinase (MMP) activity secondary to volume overload. Additionally, we investigated the overall functional outcome of preventative endothelin receptor antagonism during 14 days of chronic volume overload. LV tissue from sham-operated (Sham), untreated-fistula (Fist), and bosentan (100 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 )-treated animals (Fist ϩ Bos) was analyzed for mast cell density, MMP activity, and myocardial collagen volume fraction at 1 and 5 days after the creation of an aortocaval fistula. When compared with untreated fistulas, bosentan treatment prevented the marked increase in LV mast cell density at 1 day postfistula (3.1 Ϯ 0.3 vs. 1.3 Ϯ 0.3 LV mast cells/mm 2 , Fist vs. Fist ϩ Bos, P Յ 0.01). Additionally, the substantial increase in MMP-2 activation in the untreated fistula at 1 day was prevented following bosentan treatment (1.6 Ϯ 0.3 vs. 0.9 Ϯ 0.1 arbitrary activity units, Fist vs. Fist ϩ Bos, P Յ 0.01). The marked decrease in collagen volume fraction seen in the Fist group (1.4 Ϯ 0.1 vs. 0.8 Ϯ 0.1% myocardial tissue, Sham vs. Fist, P Յ 0.01) was significantly attenuated following bosentan treatment at both the 1-and 5-day time points. Lastly, a 2-wk preventative treatment with bosentan resulted in significant attenuation of the increase in LV end-systolic and -diastolic volumes compared with those in untreated fistula hearts. In summary, nonselective ET-1 antagonism prevents the acute increases in cardiac mast cell density and MMP activation induced secondary to chronic volume overload. By preventing these events, ET-1 antagonism was efficacious in attenuating ventricular dilatation and limiting the development of structural and functional deficits in the first 2 wk of chronic volume overload. Accordingly, these results are the first to demonstrate that cardiac mast cells are responsive to the endogenous endothelin system in vivo. Another novel finding from this study is that chronic nonspecific endothelin antagonism may inadvertently potentiate ET-1-mediated signaling.bosentan; heart; extracellular matrix; cardiac function DISCOVERED ONLY 16 years ago, the neurohormone endothelin-1 (ET-1) has been intensely investigated due to its potent cardiovascular effects and strong association with the pathophysiological worsening of cardiac function in congestive heart failure (7,13,16,29,35). ET-1 is a 21 amino acid peptide predominantly synthesized and secreted by endothelial cells. The effects of ET-1 are dictated by binding to one of two G protein-linked receptor subtypes A or B (ET A or ET B ) (16). In th...

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 85%

Section: Experimental Designmentioning

confidence: 98%

mentioning

confidence: 99%

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Effects of nonselective endothelin-1 receptor antagonism on cardiac mast cell-mediated ventricular remodeling in rats

Murray

Gardner²,

Brower³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Furthermore, mast cells are important sources of TGF-β [229], bFGF [230], and Vascular Endothelial Growth Factor (VEGF) [231], factors that can regulate fibroblast growth, modulate extracellular matrix metabolism and stimulate angiogenesis [232]. Mast cells may also influence healing and tissue remodeling by expressing gelatinases A and B [233][234][235] which are implicated in extracellular matrix metabolism. Finally, an important role for the chymase pathway in promoting angiotensin II generation and cardiac fibrosis has been suggested [236].…”

Section: The Mast Cellsmentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

561

489

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Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration.

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Cardiac Fibroblast Physiology and Pathology

Dostal

Glaser

Baudino

2015

Comprehensive Physiology

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Cardiac function is mediated by interactions between the cellular constituents of the heart, as well as the extracellular matrix. The major cell types of the heart include cardiac fibroblasts, myocytes, endothelial cells, and vascular smooth muscle cells. In addition, there are also resident stem cells and transient cell types, such as immune cells. Interactions in the heart include chemical, mechanical, and electrical signals, which vary depending on the developmental stage, disease state, and specific cell type. Understanding how these different signals interact at the molecular, cellular, and organ levels is important for better understanding cardiac function under a variety of physiological and pathological conditions. Cardiac fibroblasts play key roles in maintaining normal cardiac form and function, as well as in the cardiac remodeling process during pathological conditions, such as myocardial infarction and hypertension. Regardless of normal or pathological status of the heart, fibroblasts have multiple functions, such as synthesis and deposition of extracellular matrix and cell-cell communication with other cardiac cells, including myocytes and endothelial cells. Interactions with other cell types can affect multiple cell signaling pathways (e.g., ERK, JNK, and p38), the expression and secretion of numerous growth factors and cytokines, microRNA exchange, gene and protein expression, and angiogenesis. In this review, we provide insight into the cardiac fibroblast under normal and pathological conditions to illustrate their importance in maintaining proper cardiac function.

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Cause and effect relationship between myocardial mast cell number and matrix metalloproteinase activity

Cited by 124 publications

References 35 publications

Effects of nonselective endothelin-1 receptor antagonism on cardiac mast cell-mediated ventricular remodeling in rats

Effects of nonselective endothelin-1 receptor antagonism on cardiac mast cell-mediated ventricular remodeling in rats

The immune system and cardiac repair

Cardiac Fibroblast Physiology and Pathology

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