Structural basis of end-stage failure in ischemic cardiomyopathy in humans.

Beltrami, Carlo Alberto; Finato, Nicoletta; Rocco, Maurizio; Feruglio, G A; Puricelli, C; Cigola, Elena; Quaini, Federico; Sonnenblick, E H; Olivetti, G; Anversa, Piero

doi:10.1161/01.cir.89.1.151

Cited by 522 publications

(340 citation statements)

References 48 publications

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“…The changes in cardiac anatomy acutely after infarction, in combination with elevated filling pressure and decreased systolic pressure, induce large increases in diastolic stress and modest increases in systolic stress (18,31). These structural-functional modifications promote chronic remodeling and the evolution of the myopathy to terminal failure (19,31). Formation of new myocardium within the infarct attenuated the anatomical alterations, led to chronic increases in EF, and reduced the abnormalities in cavitary pressure, contractility, and loading.…”

Section: Discussionmentioning

confidence: 99%

“…Only longitudinally oriented cells with centrally located nuclei were included. The length and diameter across the nucleus were collected in each M to compute cell volume, assuming a cylindrical shape (18,19). M were divided in classes, and the number of M in each class was calculated from the quotient of total M class volume and average cell volume (20,21).…”

Section: Methodsmentioning

confidence: 99%

“…M were divided in classes, and the number of M in each class was calculated from the quotient of total M class volume and average cell volume (20,21). The number of arteriole and capillary profiles per unit area of myocardium was measured as described (18,19).…”

Section: Methodsmentioning

confidence: 99%

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Mobilized bone marrow cells repair the infarcted heart, improving function and survival

Orlic

Kajstura

Chimenti

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

1,901

1,304

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Attempts to repair myocardial infarcts by transplanting cardiomyocytes or skeletal myoblasts have failed to reconstitute healthy myocardium and coronary vessels integrated structurally and functionally with the remaining viable portion of the ventricular wall. The recently discovered growth and transdifferentiation potential of primitive bone marrow cells (BMC) prompted us, in an earlier study, to inject in the border zone of acute infarcts Lin ؊ c-kit POS BMC from syngeneic animals. These BMC differentiated into myocytes and vascular structures, ameliorating the function of the infarcted heart. Two critical determinants seem to be required for the transdifferentiation of primitive BMC: tissue damage and a high level of pluripotent cells. On this basis, we hypothesized here that BMC, mobilized by stem cell factor and granulocyte-colony stimulating factor, would home to the infarcted region, replicate, differentiate, and ultimately promote myocardial repair. We report that, in the presence of an acute myocardial infarct, cytokine-mediated translocation of BMC resulted in a significant degree of tissue regeneration 27 days later. Cytokineinduced cardiac repair decreased mortality by 68%, infarct size by 40%, cavitary dilation by 26%, and diastolic stress by 70%. Ejection fraction progressively increased and hemodynamics significantly improved as a consequence of the formation of 15 ؋ 10 6 new myocytes with arterioles and capillaries connected with the circulation of the unaffected ventricle. In conclusion, mobilization of primitive BMC by cytokines might offer a noninvasive therapeutic strategy for the regeneration of the myocardium lost as a result of ischemic heart disease and, perhaps, other forms of cardiac pathology.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Mobilized bone marrow cells repair the infarcted heart, improving function and survival

Orlic

Kajstura

Chimenti

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

1,901

1,304

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“…The first condition is encountered in dilated cardiomyopathy and in nonocclusive coronary artery constriction, whereas the second is found after occlusion of a major epicardial coronary artery and acute myocardial infarction . Cell death, which is also distributed nonhomogeneously in the surviving Fiordaliso et al myocardium after infarction, has significant consequences on the progression of ischemic myopathy to end-stage cardiac failure (Beltrami et al, 1994). Experimental results strongly support this contention (Cheng et al, 1996a).…”

Section: Diabetes and Cardiac Functionmentioning

confidence: 93%

Myocyte Death in Streptozotocin-Induced Diabetes in Rats Is Angiotensin II- Dependent

Fiordaliso

Latini

et al. 2000

Laboratory Investigation

276

217

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SUMMARY:To determine whether myocyte death and angiotensin II (AT II) formation are implicated in the development of diabetic cardiomyopathy, rats were injected with streptozotocin, and apoptosis and necrosis were measured at 3, 10, and 28 days. Expression of the components of the renin-angiotensin system (RAS) and AT II levels were assessed at 3 days. The percentage of AT II-labeled myocytes and the number and distribution of AT II sites in myocytes were measured at 3 and 10 days. The effects of AT 1 blockade on local RAS and cell death were examined at 3 days. Diabetes was characterized by myocyte apoptosis that peaked at 3 days and decreased at 10 and 28 days, in spite of high concentrations of blood glucose. Cell necrosis was absent throughout. Angiotensinogen, renin, and AT 1 receptor increased in myocytes from diabetic rat hearts, while angiotensin-converting enzyme and AT 2 remained constant. AT II quantity increased severalfold, as did the fraction of AT II positive cells and the number of AT II sites per myocyte. However, AT II labeling decreased at 10 days, which paralleled the reduction in myocyte death. AT 1 antagonist inhibited upregulation of this receptor and angiotensinogen, which prevented AT II synthesis and myocyte death at their peaks with diabetes. An aggregate 30% myocyte loss and a 14% increase in the volume of viable cells were found in diabetic rats at 28 days. Thus diabetic cardiomyopathy may be viewed as an AT II-dependent process in which that peptide plays a critical role in myocyte death and hypertrophy. (Lab Invest 2000, 80:513-527).

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“…Cependant, cette dégradation est nécessaire à la cicatrisation, comme le démontre les travaux d'Heymans et al et de Creemers et al menés chez des souris génétiquement modifiées [12,17], et il est donc capital de ne pas la bloquer entièrement. L'accumulation chronique de collagène dans les semaines et les mois qui suivent l'infarctus représente cependant une menace importante pour la fonction ventriculaire [28], mais qui est maintenant minimisée par l'utilisation théra-peutique des inhibiteurs du système rénine-angiotensine-aldostérone. …”

Section: Remodelage De La Matrice Extracellulaireunclassified