Myocardial infarction and remodeling in mice: effect of reperfusion

Michael, Lloyd H.; Ballantyne, Christie M.; Zachariah, Justin P.; Gould, Kenneth E.; Pocius, Jennifer; Taffet, George E.; Hartley, Craig J.; Pham, Thuy T.; Daniel, Sherita L.; Funk, Etai; Entman, Mark L.

doi:10.1152/ajpheart.1999.277.2.h660

Cited by 93 publications

(138 citation statements)

References 42 publications

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“…We used a previously published method adopted to arrest hearts of inducible mutant mice or controls in diastole and fix them in 10% formalin (50). Five-micrometer sections of formalin-fixed, paraffin-embedded tissue were used for TUNEL assay, H&E staining, Masson's trichrome staining, and immunohistochemistry.…”

Section: Methodsmentioning

confidence: 99%

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Chintalgattu¹,

Ai²,

Langley³

et al. 2010

J. Clin. Invest.

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173

140

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PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-β expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to loadinduced stress resulted in cardiac dysfunction and heart failure. Mechanistically, we showed that cardiomyocyte PDGFR-β signaling plays a vital role in stress-induced cardiac angiogenesis. Specifically, we demonstrated that cardiomyocyte PDGFR-β was an essential upstream regulator of the stress-induced paracrine angiogenic capacity (the angiogenic potential) of cardiomyocytes. These results demonstrate that cardiomyocyte PDGFR-β is a regulator of the compensatory cardiac response to pressure overload-induced stress. Furthermore, our findings may provide insights into the mechanism of cardiotoxicity due to anticancer PDGFR inhibitors.

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Section: Methodsmentioning

confidence: 99%

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Chintalgattu¹,

Ai²,

Langley³

et al. 2010

J. Clin. Invest.

Self Cite

173

140

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“…For assessment of cardiac remodeling after infarction, sham-operated and 7-dayreperfused hearts were perfusion fixed as described by Michael et al (36). Briefly, cardioplegic solution was perfused through the jugular vein to promote relaxation, the heart was excised and rinsed in cold cardioplegic solution, the aorta was cannulated, and a PE-50 catheter was pushed through the mitral valve into the LV and secured in place.…”

Section: Methodsmentioning

confidence: 99%

Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction

Thakker

Frangogiannis

Bujak

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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105

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Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction. Am J Physiol Heart Circ Physiol 291: H2504 -H2514, 2006. First published May 26, 2006 doi:10.1152/ajpheart.00322.2006.-Epidemiological studies indicate that obesity, insulin resistance, and diabetes are important comorbidities of patients with ischemic heart disease and increase mortality and development of congestive heart failure after myocardial infarction. Although ob/ob and db/db mice are commonly used to study obesity with insulin resistance or diabetes, mutations in the leptin gene or its receptor are rarely the cause of obesity in humans, which is, instead, primarily a consequence of dietary and lifestyle factors. Therefore, we used a murine model of diet-induced obesity to examine the physiological effects of obesity and the inflammatory and healing response of diet-induced obese (DIO) mice after myocardial ischemia-reperfusion injury. DIO mice developed hyperinsulinemia and insulin resistance and hepatic steatosis, with significant ectopic lipid deposition in the heart and cardiac hypertrophy in the absence of significant changes in blood pressure. The mRNA levels of chemokines at 24 h and cytokines at 24 and 72 h of reperfusion were higher in DIO than in lean mice. In granulation tissue at 72 h of reperfusion, macrophage density was significantly increased, whereas neutrophil density was reduced, in DIO mice compared with lean mice. At 7 days of reperfusion, collagen deposition in the scar was significantly reduced and left ventricular (LV) dilation and cardiac hypertrophy were increased, indicative of adverse LV remodeling, in infarcted DIO mice. Characterization of a murine diet-induced model of obesity and insulin resistance that satisfies many aspects commonly observed in human obesity allows detailed examination of the adverse cardiovascular effects of diet-induced obesity at the molecular level. insulin resistance; cardiac lipotoxicity; ischemia-reperfusion injury; left ventricular remodeling THE INCIDENCE OF OVERWEIGHT and obesity in the Western world has risen dramatically; in the United States, two-thirds of the adult population is overweight and one-third is obese (27). Extreme obesity is known to impact the structure and function of the heart in terms of hemodynamic load, altered left ventricular (LV) remodeling, and impaired ventricular function leading to overt heart failure (30, 31). In at least four community-based, prospective studies, body mass index (BMI) incrementally predicted heart failure risk above and beyond known risk factors for heart failure. Obesity is known to independently increase the risk for hypertension, diabetes, and dyslipidemia, all of which increase the risk for myocardial infarction and subsequent heart failure. On the other hand, when associated with fewer comorbidities, obesity paradoxically has been found to be protective in the short term after a myocardial infarction (39). Nonetheless, the risks for recurrent myocardial infarction and adverse outcome in the long term...

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“…Sham animals (n=8) were used as controls. A cardioplegic solution (Michael et al 1999) was perfused through the jugular vein to promote relaxation. After excision and rinsing in cold cardioplegic solution, two PE-50 catheters were pushed into the left ventricle (one through the aorta, the other through the left atrium), secured in place, and used to enable flow of fixative through the left ventricle.…”

Section: Perfusion Fixation and Assessment Of Ventricular Volumesmentioning

confidence: 99%

Systematic Characterization of Myocardial Inflammation, Repair, and Remodeling in a Mouse Model of Reperfused Myocardial Infarction

Christia

Bujak

González-Quesada

et al. 2013

J Histochem Cytochem.

103

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Mouse models of myocardial infarction are essential tools for the study of cardiac injury, repair, and remodeling. Our current investigation establishes a systematic approach for quantitative evaluation of the inflammatory and reparative response, cardiac function, and geometry in a mouse model of reperfused myocardial infarction. Reperfused mouse infarcts exhibited marked induction of inflammatory cytokines that peaked after 6 hr of reperfusion. In the infarcted heart, scar contraction and chamber dilation continued for at least 28 days after reperfusion; infarct maturation was associated with marked thinning of the scar, accompanied by volume loss and rapid clearance of cellular elements. Echocardiographic measurements of end-diastolic dimensions correlated well with morphometric assessment of dilative remodeling in perfusion-fixed hearts. Hemodynamic monitoring was used to quantitatively assess systolic and diastolic function; the severity of diastolic dysfunction following myocardial infarction correlated with cardiomyocyte hypertrophy and infarct collagen content. Expression of molecular mediators of inflammation and cellular infiltration needs to be investigated during the first 72 hr, whereas assessment of dilative remodeling requires measurement of geometric parameters for at least four weeks after the acute event. Rapid initiation and resolution of the inflammatory response, accelerated scar maturation, and extensive infarct volume loss are important characteristics of infarct healing in mice.

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Myocardial infarction and remodeling in mice: effect of reperfusion

Cited by 93 publications

References 42 publications

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction

Systematic Characterization of Myocardial Inflammation, Repair, and Remodeling in a Mouse Model of Reperfused Myocardial Infarction

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