Regulation of collagen degradation in the rat myocardium after infarction

Cleutjens, Jack P.M.; Kandala, Jagannadha C.; Guarda, Eduardo; Guntaka, Ramareddy V.; Weber, Karl T.

doi:10.1016/s0022-2828(05)82390-9

Cited by 440 publications

(280 citation statements)

References 41 publications

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“…TGF-β also stimulates the synthesis of TIMPs. TIMPs primarily inhibit collagen degradation by matrix metalloproteinases and therefore facilitate collagen accumulation (34). TIMP expression is tightly controlled at the transcription level.…”

Section: Discussionmentioning

confidence: 99%

Cardiac oxidative stress and remodeling following infarction: role of NADPH oxidase

Zhao¹,

Zhao²,

Yan³

et al. 2009

Cardiovascular Pathology

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Background-There is growing recognition that oxidative stress plays a role in the pathogeneses of myocardial repair/remodeling following infarction (MI). NADPH oxidase is a major source for cardiac reactive oxygen species production. Herein, we studied the importance of NADPH oxidase in development of cardiac oxidative stress and its induced molecular and cellular changes related to myocardial repair/remodeling.

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Section: Discussionmentioning

confidence: 99%

Cardiac oxidative stress and remodeling following infarction: role of NADPH oxidase

Zhao¹,

Zhao²,

Yan³

et al. 2009

Cardiovascular Pathology

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“…22 The temporal sequence of collagen degradation by the MMPs is species-specific. 7,23 Collagen breakdown begins within 3 hours of infarction and is induced by serine proteases such as plasmin and the release of MMP8 from neutrophils. 7 The initial digestion of collagen intercellular struts is responsible for the slippage of the necrotic myofilaments that causes infarct expansion.…”

Section: Collagen Degradationmentioning

confidence: 99%

“…1,6 Early Remodeling Infarct expansion results from the degradation of the intermyocyte collagen struts by serine proteases and the activation of matrix metalloproteinases (MMPs) released from neutrophils. 7 Infarct expansion occurs within hours of myocyte injury, 3 results in wall thinning and ventricular dilatation, and causes the elevation of diastolic and systolic wall stresses. Early ventricular dilatation due to infarct expansion has been unequivocally demonstrated in man.…”

mentioning

confidence: 99%

Left Ventricular Remodeling After Myocardial Infarction

2000

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L eft ventricular remodeling is the process by which ventricular size, shape, and function are regulated by mechanical, neurohormonal, and genetic factors. 1,2 Remodeling may be physiological and adaptive during normal growth or pathological due to myocardial infarction, cardiomyopathy, hypertension, or valvular heart disease ( Figure 1). This article will review postinfarction remodeling, pathophysiological mechanisms, and therapeutic intervention. Pathophysiology Postinfarction Left Ventricular RemodelingThe acute loss of myocardium results in an abrupt increase in loading conditions that induces a unique pattern of remodeling involving the infarcted border zone and remote noninfarcted myocardium. Myocyte necrosis and the resultant increase in load trigger a cascade of biochemical intracellular signaling processes that initiates and subsequently modulates reparative changes, which include dilatation, hypertrophy, and the formation of a discrete collagen scar. Ventricular remodeling may continue for weeks or months until the distending forces are counterbalanced by the tensile strength of the collagen scar. This balance is determined by the size, location, and transmurality of the infarct, the extent of myocardial stunning, the patency of the infarct-related artery, and local tropic factors. 1,3 The myocardium consists of 3 integrated components: myocytes, extracellular matrix, and the capillary microcirculation that services the contractile unit assembly. Consideration of all 3 components provides important insights into the remodeling process and a rationale for future therapeutic strategies. The cardiomyocyte is terminally differentiated and develops tension by shortening. The extracellular matrix provides a stress-tolerant, viscoelastic scaffold consisting of type I and type III collagen that couples myocytes and maintains the spatial relations between the myofilaments and their capillary microcirculation. 4,5 The collagen framework couples adjacent myocytes by intercellular struts that align myofilaments to optimize force development, distribute force evenly to the ventricular walls, and prevent sarcomeric deformation. 5 Myocardial infarction results in the migration of macrophages, monocytes, and neutrophils into the infarct zone; this initiates intracellular signaling and neurohormonal activation, which localizes the inflammatory response. Changes in circulatory hemodynamics are determined primarily by the magnitude of myocyte loss, the stimulation of the sympathetic nervous system and renin-angiotensin-aldosterone system, and the release of natriuretic peptides.Postinfarction remodeling has been arbitrarily divided into an early phase (within 72 hours) and a late phase (beyond 72 hours). The early phase involves expansion of the infarct zone, 5 which may result in early ventricular rupture or aneurysm formation. Late remodeling involves the left ventricle globally and is associated with time-dependent dilatation, the distortion of ventricular shape, and mural hypertrophy. The failure to normalize increa...

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“…These phenotypically modulated fibroblasts, termed myofibroblasts [240][241][242] develop ultrastructural and phenotypic characteristics of smooth muscle cells and possess a contractile apparatus that contains bundles of actin myofilaments with associated contractile proteins, such as nonmuscle myosin [243]. Myofibroblasts are the predominant source of collagen mRNA in healing myocardial infarcts [244][245][246], [247]. They transiently appear during granulation tissue formation and become apoptotic when the scar matures [248].…”

Section: The Mast Cellsmentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

572

499

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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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Regulation of collagen degradation in the rat myocardium after infarction

Cited by 440 publications

References 41 publications

Cardiac oxidative stress and remodeling following infarction: role of NADPH oxidase

Cardiac oxidative stress and remodeling following infarction: role of NADPH oxidase

Left Ventricular Remodeling After Myocardial Infarction

The immune system and cardiac repair

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