In vivo collagen turnover during development of thyroxine-induced left ventricular hypertrophy

Karim, M.Asad; Ferguson, Alan; Wakim, Bassam T.; Samarel, Allen M.

doi:10.1152/ajpcell.1991.260.2.c316

Cited by 33 publications

(20 citation statements)

References 18 publications

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“…To further examine the relationships between myocardial collagen content and steady state mRNA levels for procollagen polypeptides during LV pressure overload, the proline constant infusion method ( 15,16,24) was used to assess procollagen biosynthesis at 1, 4, and 16 wk after suprarenal aortic coarctation. As seen in Table II, procollagen synthetic rates (Rs; gg/d per LV) in sham versus banded animals were similar 1 and 4 wk after aortic coarctation.…”

Section: Resultsmentioning

confidence: 99%

“…This biosynthetic labeling method allows for the accurate measurement of procollagen synthesis in the intact animal, as well as an estimate of the proportion of newly synthesized cardiac procollagens subject to rapid intracellular degradation (4). Thus the amounts of fully processed collagens that are ultimately secreted and deposited in the extracellular space can be determined ( 15). Evidence is presented in this report to indicate that alterations in procollagen synthesis and intracellular degradation are both important in the complex regulatory events responsible for cardiac extracellular matrix remodeling during sustained hypertension.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of procollagen metabolism in the pressure-overloaded rat heart.

Eleftheriades¹,

Durand²,

Ferguson³

et al. 1993

J. Clin. Invest.

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To determine the molecular events responsible for the disproportionate accumulation of myocardial fibrillar collagens during sustained hypertension, we examined the in vivo rate of procollagen synthesis, collagen accumulation, and intracellular procollagen degradation 1-16 wk after abdominal aortic banding in young rats. These measurements were correlated with tissue mRNA levels for type I and type III procollagen polypeptides. Banded animals developed moderate, sustained hypertension and mild left ventricular hypertrophy. Increased type III procollagen mRNA levels were detected early after banding and persisted for the entire observation period. Disproportionate collagen accumulation without histological evidence of fibrosis was noted within 1 wk after hypertension induction. Fibrillar collagen accumulation at this time point resulted not from a major increase in procollagen synthesis, but rather a marked decrease in the rate of intracellular procollagen degradation. Interstitial fibrosis, however, was observed 16 wk after banding. Type I procollagen mRNA levels were increased sixfold, but only after 16 wk of hypertension. These results correlated well with the results of in vivo procollagen synthesis experiments at 16 wk, which demonstrated a threefold increase in left ventricular procollagen biosynthesis. We conclude that pretranslational as well as posttranslational mechanisms regulate fibrillar collagen deposition in the myocardial extracellular matrix during sustained hypertension. (J. Clin. Invest. 1993.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of procollagen metabolism in the pressure-overloaded rat heart.

Eleftheriades¹,

Durand²,

Ferguson³

et al. 1993

J. Clin. Invest.

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“…A spectrophotometric method was used to assess urine hydroxyproline, taken as a rough index of collagen turnover. 27 To avoid interference with the colorimetric method used, all subjects studied received a specific diet without meat, fish, and ice cream for 3 days before urine collection. In our laboratory, intra-assay and interassay coefficients of variation for urine hydroxyproline were 4.5% and 6.3%, respectively,…”

Section: Determination Of Humoral Profilementioning

confidence: 99%

Myocardial Ultrasonic Backscatter in Hypertension

et al. 2003

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Abstract-A disproportionate accumulation of fibrillar collagen is a characteristic feature of hypertensive heart disease, but the extent of myocardial fibrosis may differ in different models of hypertension. In experimental studies, aldosterone and endothelins emerge as important determinants of myocardial fibrosis. Changes in myocardial extracellular matrix and collagen deposition can be estimated noninvasively by analysis of the ultrasonic backscatter signal, which arises from tissue heterogeneity within the myocardium and describes myocardial texture. This study was designed to investigate the relations between myocardial integrated backscatter and circulating aldosterone and immunoreactive endothelin in human hypertension. The study population consisted of 56 subjects: 14 healthy normotensive volunteers and 42 hypertensive patients (14 with primary aldosteronism, 7 with renovascular hypertension, and 21 with essential hypertension). The patients with essential and secondary hypertension were matched for age, gender, body mass index, and blood pressure. Myocardial integrated backscatter at diastole was 19.8Ϯ2.0 and 20.8Ϯ2.9 decibels in normotensive control subjects and patients with essential hypertension and significantly higher in patients with primary aldosteronism (27.4Ϯ3.8 decibels, PϽ0.01) and renovascular hypertension (26.8Ϯ4.8 decibels, PϽ0.01). In the population as a whole, as well as in the hypertensive subpopulation, myocardial integrated backscatter was directly related to plasma aldosterone (rϭ0.73 and 0.71, PϽ0.01 for both) and immunoreactive endothelin (rϭ0.60 and 0.56, PϽ0.01 for both). The data of this study suggest that in human hypertension, circulating aldosterone and immunoreactive endothelin may induce alterations in left ventricular myocardial texture, possibly related to increased myocardial collagen content.

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“…For instance, following myocardial infarction, early-phase remodeling is often characterized by an initial degradation of the left ventricular (LV) collagen network [4] and late-phase remodeling is accompanied by excessive collagen accumulation [5]. Whereas, remodeling in pressure overload states includes a slower progression to cardiac fibrosis, specifically interstial fibrillar collagen deposition, resulting in dysfunctional chamber filling during diastole [6]. The connection between obesity and cardiovascular disease is well-established and is supported by numerous epidemiological studies [7,8].…”

Section: Introductionmentioning

confidence: 99%

Leptin regulates MMP-2, TIMP-1 and collagen synthesis via p38 MAPK in HL-1 murine cardiomyocytes

Schram

Girolamo

Madani

et al. 2010

Cellular and Molecular Biology Letters

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Abbreviations used: AP-1 -activator protein-1; ATF-2 -activating transcription factor-2; ECM -extracellular matrix; HF-heart failure; LV -left ventricular; MAPK -mitogen activated protein kinase; MMP -matrix metalloproteinase; mRNA-messenger ribonucleic acid; PBS -phosphate buffered saline; PCR -polymerase chain reaction; TIMP-tissue inhibitor of metalloproteinase Abstract: A clear association between obesity and heart failure exists and a significant role for leptin, the product of the obese gene, has been suggested. One aspect of myocardial remodeling which characterizes heart failure is a disruption in the balance of extracellular matrix synthesis and degradation. Here we investigated the effects of leptin on matrix metalloproteinase (MMP) activity, tissue inhibitor of metalloproteinase (TIMP) expression, as well as collagen synthesis in HL-1 cardiac muscle cells. Gelatin zymographic analysis of MMP activity in conditioned media showed that leptin enhanced MMP-2 activity in a dose-and time-dependent manner. Leptin is known to stimulate phosphorylation of p38 MAPK in cardiac cells and utilization of the p38 MAPK inhibitor, SB203580, demonstrated that this kinase also plays a role in regulating several extracellular matrix components, such that inhibition of p38 MAPK signaling prevented the leptin-induced increase in MMP-2 activation. We also observed that leptin enhanced collagen synthesis determined by both proline incorporation and picrosirius red staining of conditioned media. Pro-collagen type-I and pro-collagen type-III expression, measured by real-time PCR and Western blotting were also increased by leptin, effects which were again attenuated by SB203580. In summary, these results demonstrate the potential for leptin to play a role in mediating myocardial ECM remodeling and that the p38 MAPK pathway plays an important role in mediating these effects.

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In vivo collagen turnover during development of thyroxine-induced left ventricular hypertrophy

Cited by 33 publications

References 18 publications

Regulation of procollagen metabolism in the pressure-overloaded rat heart.

Regulation of procollagen metabolism in the pressure-overloaded rat heart.

Myocardial Ultrasonic Backscatter in Hypertension

Leptin regulates MMP-2, TIMP-1 and collagen synthesis via p38 MAPK in HL-1 murine cardiomyocytes

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