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Results for “ENDOMYOCARDIAL FIBROSIS”

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PubMedDate not supplied

Induction of cardiac fibrosis by transforming growth factor-beta(1).

The role of transforming growth factor-beta(1) (TGF-beta(1)) in the production and deposition of collagens and in the induction of gene expression in the myocardium in relation to the development of myocardial fibrosis will be discussed. Very low expression of TGF-beta(1) and collagen type I and III mRNA is seen in the normal rat heart. Both expressions are markedly increased in the infarcted heart and the levels of TGF-beta(1) mRNA precedes increases in mRNA levels for extracellular matrix (ECM) proteins, suggesting a possible role of TGF-beta(1) in remodeling processes in the myocardium. The TGF-beta(1) expression is normally only transient since continuous TGF-beta(1) overexpression seems to promote nonadaptive cardiac hypertrophy and myocardial fibrosis. In vitro, TGF-beta(1) induces an increase in collagen production and secretion and enhances the abundance of mRNA levels for collagen type I and III in rat cardiac fibroblasts in culture. TGF-beta(1) also stimulates in vivo the expression of ECM proteins and in vivo gene transfer of TGF-beta(1) can induce myocardial fibrosis. Increased myocardial TGF-beta(1) and ECM protein mRNA are found in myocardial fibrosis induced by angiotensin II infusion, by noradrenaline treatment, by isoprenaline infusion, and by long-term blockade of NO synthesis. In vivo antagonism of TGF-beta(1) by neutralizing anti-TGF-beta(1) antibodies or by proteoglycans prevents the increase in gene expression of ECM proteins and inhibits myocardial fibrosis, suggesting that the increases in matrix protein production and fibrosis are mediated by TGF-beta(1).

Angiotensin II↗
PubMed2004

Matrix metalloproteinases and their tissue inhibitors in pressure-overloaded human myocardium during heart failure progression.

OBJECTIVES: We studied the role of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in fibrosis formation in the transition from hypertrophy to heart failure (HF) as well as the cellular source of MMPs and TIMPs. BACKGROUND: Human pressure-overloaded hearts are characterized by a significant increase in cardiac fibrosis. However, the contribution of the proteolytic/antiproteolytic system in aortic stenosis (AS) during hypertrophy progression has not yet been elucidated. METHODS: Three groups of AS patients (I: EF >50%, n = 12; II: EF 50% to 30%, n = 10; III: EF <30%, n = 12) undergoing aortic valve replacement and seven controls were studied. Tissue samples were investigated by immunoconfocal microscopy, Western blotting, and zymography. RESULTS: Quantitative analysis by immunoconfocal microscopy and Western blotting showed an upregulation of MMP-1, -2, -3, -9, -13, and -14 in group I and further increases in later stages. Tissue inhibitors of metalloproteinase-1 and -2 were enhanced and TIMP-4 was decreased in comparison to control. Gelatinolytic activity of MMP-2 significantly (p < 0.05) increased 1.2-fold (group I), 1.5-fold (group II), and 1.6-fold (group III) over control. The level of collagen I was significantly upregulated in all AS groups. Immunoconfocal microscopy showed that MMPs and TIMPs are produced predominantly by fibroblasts. The number of proliferating fibroblasts was significantly elevated during the transition to HF (0.67 n/mm(2)-control, 5.03-group III, p < 0.05). CONCLUSIONS: In human hearts a continuous turnover of the extracellular matrix occurs during the progression from compensated hypertrophy to HF that is characterized by the upregulation of MMPs and inadequate inhibition by TIMPs. The altered balance between proteolysis/antiproteolysis with accompanying proliferation of fibroblasts results in fibrosis progression.

Aged↗
PubMed1997

Fibromuscular dysplasia of small coronary arteries and fibrosis in the basilar ventricular septum in mitral valve prolapse.

The mechanism of sudden cardiac death in patients with mitral valve prolapse is poorly understood. Twenty-four hearts from patients with mitral valve prolapse who suddenly died (mean age 34 +/- 8 years) and 16 trauma control hearts (mean age 30 +/- 7 years) were histologically studied. Dysplasia of the atrioventricular nodal artery was present in 18 of 24 hearts with mitral valve prolapse and four of 16 controls hearts (p = 0.003). The degree of luminal narrowing, as morphometrically measured, was significantly greater in hearts with mitral valve prolapse (p = 0.003). The degree of fibrosis in the base of the ventricular septum, as calculated by computerized morphometry, was greater in hearts with mitral valve prolapse (p = 0.0002) and independent of age, sex, and heart weight (p = 0.005). We conclude that arterial dysplasia in mitral valve prolapse may contribute to sudden cardiac death mediated by ventricular fibrosis.

Adult↗
PubMed1992

Mineralocorticoid excess, dietary sodium, and myocardial fibrosis.

Unlike the non-renin-dependent hypertension associated with infrarenal aorta banding, an abnormal accumulation of fibrillar collagen occurs within the adventitia of intramural coronary arteries and neighboring interstitial space of the left and right ventricles in arterial hypertension associated with primary or secondary hyperaldosteronism. Based on these findings it was suggested that this interstitial and perivascular fibrosis was mediated by mineralocorticoid excess (i.e., elevated plasma aldosterone relative to dietary sodium) and not ventricular loading. To further address the importance of mineralocorticoid excess, we examined the fibrous tissue response after 8 weeks in the following uninephrectomized rat groups receiving a high-sodium diet: D-aldosterone (ALDO) infusion (0.75 micrograms/hr sc, n = 16); deoxycorticosterone acetate (DOCA) administration (100 mg/kg/wk sc, n = 8); and administration of a mineralocorticoid-like substance, glycyrrhizic acid (GA; 1 gm kg/wk sc, n = 8). Compared with ALDO infusion and sodium deprivation (n = 9), untreated controls (n = 14), and uninephrectomized rats with high dietary sodium and no mineralocorticoid administration (n = 15), we found (1) hypertension and left ventricular hypertrophy with all forms of mineralocorticoid excess; (2) a rise in collagen volume fraction with ALDO, and an increase in perivascular collagen with DOCA; and (3) no observance of myocardial fibrosis with GA or experimental controls, including ALDO infusion and sodium deprivation. Thus, in the presence of enhanced sodium intake, chronic administration of ALDO or DOCA are associated with collagen accumulation in the myocardium, whereas with the mineralocorticoid-like compound GA, myocardial fibrosis was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1998

Assessment of myocardial fibrosis in cardiomyopathic hamsters with gadolinium-DTPA enhanced magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The authors investigated whether magnetic resonance (MR) imaging enhanced with gadolinium (Gd)-DTPA would be useful for assessment of myocardial fibrosis in cardiomyopathy. METHODS: The authors compared MR images of the excised heart after Gd-DTPA injection with histopathologic findings in 33 hamsters with cardiomyopathy of the Bio 14.6 strain and 26 healthy hamsters of various age groups and assessed localization of Gd-14C-DTPA by autoradiography in the myocardium of three hamsters with cardiomyopathy. RESULTS: The mean signal intensity ratios for the entire myocardium in hamsters with cardiomyopathy relative to that in healthy hamsters was significantly higher in a younger age group than in an older age group (1.30+/-0.09 versus 1.03+/-0.08, P < 0.001, respectively). This myocardial enhancement was more obvious in areas containing massive fibrosis in the early and mid stages than in the late stage. Autoradiograms of hamsters with cardiomyopathy showed patchy or linear increases in uptake, corresponding to the areas of myocardial fibrosis. Gadolinium-14C-DTPA radioactivity ratios of myocardial fibrosis to healthy myocardium were significantly higher in the early and mid stages than in the late stage (P < 0.01). CONCLUSIONS: Myocardial fibrosis with high cellularity and proliferation of vessels was delineated as an area enhanced with Gd-DTPA on MR images, and its signal intensity decreased with the late stage of myocardial fibrosis.

Analysis of Variance↗
PubMed1993

CT and MR evaluation of pericardial constriction: a new diagnostic and therapeutic concept.

Eighty patients with pericardial constriction confirmed by catheter data were studied by CT (n = 79), MR imaging (n = 24), or both. To determine the validity of these imaging methods for subsequent treatment, 30 patients' studies were evaluated retrospectively (1980-1984) and 50 (1985-1991) prospectively. Twenty patients from the first group and 30 patients from the second group underwent pericardiectomy. By systematic analysis of CT scans and MR images it was possible to characterize the morphology of pericardial constriction (n = 80); to identify global (n = 27), right-sided (n = 46), left-sided (n = 2), annular (n = 2), effusive (n = 2), and epicardial (n = 1) forms of pericardial constriction; and to define parameters of myocardial atrophy and fibrosis (n = 17). Seventeen patients had myocardial atrophy, fibrosis, or both. Seven of them underwent pericardiectomy; all died of acute myocardial failure (100%). Four (9.3%) of 43 patients without myocardial atrophy or fibrosis died as a consequence of other complications. The method of thoracotomy and periepicardiectomy was continuously adjusted to the preoperative CT and MR findings. Thus, the clinical use of CT and MR imaging in patients with known or suspected pericardial constriction is based on (a) exclusion of patients with restrictive hemodynamics from diagnostic thoracotomy, (b) preoperative determination of the method of thoracotomy and extent of pericardiectomy, and (c) exclusion of patients with myocardial atrophy or fibrosis from pericardiectomy.

Adult↗
PubMed2005

Angiotensin AT2 receptor deficiency after myocardial infarction: its effects on cardiac function and fibrosis depend on the stimulus.

Hearts of normotensive angiotensin II type 2 receptor (AT2)-deficient mice do not develop fibrosis after angiotensin II-induced chronic hypertension. Thus, the goal of our study was to clarify whether AT2 knockouts (KOs) are also characterized by altered left ventricular (LV) function and modified remodeling of the extracellular matrix (ECM) after induction of myocardial infarction (MI). MI was induced in 5-mo-old female AT2-deficient mice and controls by occlusion of the left coronary artery. Time-matched sham-operated animals served as controls. After 48 h, the first sets of mice were hemodynamically characterized using a pressure-tip catheter (n = 8/group). We also obtained pressure volume loops using a microconductance catheter in additional sets of animals 3 wk after induction of MI (n = 7/group). Finally, the collagen index was illustrated by Sirius red staining and quantified by digital analysis. Whereas the LV function of sham-operated animals did not differ between both genotypes, the collagen index was 44% lower in KO animals. Forty-eight hours and 3 wk post-MI, systolic and diastolic LV function were impaired in both AT2-deficient and wild-type (WT) animals to the same extent by approx 45%. No differences were found between the two genotypes with respect to LV hypertrophy and the fibrosis index in the infarcted and noninfarcted areas 3 wk post-MI. While AT2-KO mice had less cardiac collagen content under basal conditions, the receptor deficiency had no significant influence on LV function at the two investigated time points after induction of MI or on the remodeling of ECM at the latter time point. Thus, hypertension-induced fibrosis is probably triggered by other control mechanisms than fibrosis induced by MI.

Animals↗
PubMed1992

Myocardial fibrosis and the renin-angiotensin-aldosterone system.

In both men and women left ventricular hypertrophy (LVH) is the major risk factor associated with the appearance of diastolic and/or systolic myocardial failure. It is not the growth of cardiac myocytes, however, that is responsible for an abnormal structural remodeling of the hypertrophied myocardium in pathologic LVH, but instead, nonmyocyte cells whose behavior and growth are altered by chronic elevations in circulating hormones. Hormone-mediated cardiac fibroblast proliferation and/or enhanced collagen synthesis, for example, account for myocardial fibrosis. The signals mediating nonmyocyte cell involvement in LVH may also involve locally generated hormones having paracrine properties. Herein we review experimental findings pertaining to the reparative and reactive fibrosis of the myocardium seen in various forms of acquired and genetic arterial hypertension, where circulating or tissue renin-angiotensin-aldosterone systems are respectively activated. These hormonal systems determine whether myocardial structure will be altered in arterial hypertension and, accordingly, if myocardial failure ensues. The mechanisms by which these hormones lead to myocardial fibrosis remain to be elucidated and correspondingly will determine if fibrosis can be effectively prevented. At the same time, experimental strategies that regress excess collagen in LVH have been identified, but need to be developed further to determine if myocardial failure, caused by fibrosis, is indeed reversible in humans.

Aldosterone↗
PubMed1976

Endocardial changes produced in Patus monkeys by the ablation of cardiac lymphatics and the administration of a plantain diet.

The effect of obliteration of the cardiac lymph drainage and prolonged feeding with a plantain diet in Patus monkeys was studied. Althout obliteration of the cardiac lymph supply produced fibroelastotic lesions the addition of a plantain diet did not usually produce much increase in cardiac fibrosis and the changes of EMF or CUO were not seen. The reasons for this are discussed.

Animals↗
PubMed1989

Hemodynamic and prognostic value of thallium-201 myocardial imaging in patients with dilated cardiomyopathy.

We studied 70 patients with dilated cardiomyopathy to determine whether extent of perfusion defect on thallium imaging could be related to the hemodynamics and prognosis of the patients. Patients were divided into three groups according to the extent of perfusion defect, i.e., Grade I: no perfusion defect (n = 19), Grade II: apical perfusion defect (n = 22), and Grade III: extensive perfusion defect (n = 29). The patients of Grade III demonstrated marked hemodynamic deterioration compared with those of Grade I and II. Three-year survival rate showed lower value in proportion to the extent of perfusion defect (P less than 0.05). Death from progressive heart failure tended to occur in patients with extensive perfusion defect (P less than 0.05). In patients of Grade III, the perfusion defect extended mainly to the posterolateral segment. Although autopsy studies showed increased fibrosis in the left ventricular wall in these patients, the extension of the fibrosis was not related to that of fibrosis. Moreover, the perfusion defect had regressed in three of 18 patients in the follow-up examination. These results indicate that the extent of perfusion defect on thallium imaging may be of value in non-invasive evaluation and prediction of the prognosis in patients with dilated cardiomyopathy. Distribution of the perfusion defect was, however, not related to that of myocardial fibrosis.

Adolescent↗
PubMed1994

Chemotherapy induced myocardial fibrosis.

Alkylating agents have a well established role in the treatment of malignant disease, with well documented side effects. This case history, however, illustrates the susceptibility to these agents shown by some patients. It is suggested that, when drug induced pneumonitis is noted, careful screening of left ventricular function should be performed in order to diagnose myocardial fibrosis and subsequent cardiac failure.

Antineoplastic Combined Chemotherapy Protocols↗