Treatment with spironolactone for 24 weeks decreases the level of matrix metalloproteinases and improves cardiac function in patients with chronic heart failure of ischemic etiology

Li, M.J.; Huang, Congxin; Okello, Emmy; Yan-hong, Tan; Salim, Mohamed

doi:10.1016/s0828-282x(09)70138-2

Cited by 29 publications

(20 citation statements)

References 17 publications

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“…8,13 It has also been useful in detecting other conditions marked by LV dilation (such as ischemic cardiomyopathy), and improvement in PICP and related biomarker profiles has been reported after spironolactone therapy for ischemic cardiomyopathy. 7 Concentric remodeling or LVH and fibrosis are hallmarks of the early cardiomyopathy phenotype in FA, so our finding of higher PICP levels with greater concentric remodeling in FA patients makes this serum collagen synthesis value a promising biomarker of subclinical myocardial disease.…”

Section: Discussionmentioning

confidence: 89%

“…The matrix's constitution depends on the balance between the production and degradation of collagen; disequilibrium leads to cardiac remodeling. 7 Collagen type I is synthesized as procollagen with a small amino terminal and a larger procollagen I carboxyterminal propeptide (PICP). The cleavage and shedding of PICP as a soluble peptide is a hallmark of collagen production in the extracellular matrix.…”

Section: Serum Versus Imaging Biomarkers In Friedreich Ataxiamentioning

confidence: 99%

“…Therefore, the PICP level has been used as a surrogate for collagen production. 7,8 Given that collagen production occurs in all forms of LV remodeling, we sought to measure PICP in patients with FA in 2 contexts: GAA expansion, by means of genetic testing; and LV remodeling and fibrosis, by means of CMR analysis.…”

Section: Serum Versus Imaging Biomarkers In Friedreich Ataxiamentioning

confidence: 99%

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Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes

Mehta¹,

Chacko²,

Jin³

et al. 2016

Texas Heart Institute Journal

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Patients with Friedreich ataxia typically die of cardiomyopathy, marked by myocardial fibrosis and abnormal left ventricular (LV) geometry. We measured procollagen I carboxyterminal propeptide (PICP), a serum biomarker of collagen production, and characterized genotypes, phenotypes, and outcomes in these patients. Twenty-nine patients with Friedreich ataxia (mean age, 34.2 ± 2.2 yr) and 29 healthy subjects (mean age, 32.5 ± 1.1 yr) underwent serum PICP measurements. Patients underwent cardiac magnetic resonance imaging and outcome evaluations at baseline and 12 months. Baseline PICP values were significantly higher in the patients than in the control group (1,048 ± 77 vs 614 ± 23 ng/mL; P <0.001); severity of genetic abnormality did not indicate severity of PICP elevation. Higher PICP levels corresponded to greater LV concentric remodeling only at baseline (r=0.37, P <0.05). Higher baseline PICP strongly indicated subsequent increases in LV end-diastolic volume (r=0.52, P=0.02). The PICP levels did not distinguish between 14 patients with evident myocardial fibrosis identified through positive late gadolinium enhancement and 15 who had no enhancement (1,067 ± 125 vs 1,030 ± 98 ng/mL; P=0.82). At 12 months, cardiac events had occurred in 3 of 14 fibrosis-positive and none of 15 fibrosis-negative patients (P=0.1); their baseline PICP levels were similar. We conclude that PICP, a serum marker of collagen synthesis, is elevated in Friedreich ataxia and indicates baseline abnormal LV geometry and subsequent dilation. Cardiac magnetic resonance and PICP warrant consideration as complementary biomarkers in therapeutic trials of Friedreich ataxia cardiomyopathy.

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Section: Discussionmentioning

confidence: 89%

Section: Serum Versus Imaging Biomarkers In Friedreich Ataxiamentioning

confidence: 99%

Section: Serum Versus Imaging Biomarkers In Friedreich Ataxiamentioning

confidence: 99%

See 1 more Smart Citation

Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes

Mehta¹,

Chacko²,

Jin³

et al. 2016

Texas Heart Institute Journal

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“…One of the many challenges is that fibrosis is a mechanism involved in a number of overlapping and/or coexisting risk and disease states and co‐morbidities48, 49 such as hypertension, chronic kidney disease, diabetes mellitus, obesity, atrial fibrillation, ischaemic heart disease, and prevalent HF, such that a number of circulating biomarkers can be present in these various conditions 26, 46, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61. Our hypothesis is that novel ‘mechanistic’ markers of cardiac fibrosis are differentially expressed in various risk and disease states and co‐morbidities.…”

Section: Discussionmentioning

confidence: 99%

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

et al. 2017

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AimsMyocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European‐Commission‐funded ‘FIBROTARGETS’ is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti‐fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure.Methods and resultsThe FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12 000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community‐based population cohorts, cardiovascular risk cohorts, and heart failure cohorts.ConclusionsThe FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific ‘fibrotic’ phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti‐fibrotic therapies for heart failure.

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“…Theoretically, some antihypertensive drugs may alter the levels of matrix metalloproteinases but it was found that enalapril has no effect on matrix metalloproteinase levels (35). Moreover, it has been reported that spironolactone treatment for 24 weeks found partially reverse the dysregulation in collagen metabolism (36).…”

Section: Matrix Metalloproteinases and Tissue Inhibitors In Pulmonarymentioning

confidence: 99%

Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases levels in pediatric patients with congenital heart disease: Relationship to cardiac functions

Kılıç

Uçar²,

Özdemir³

et al. 2014

Anadolu Kardiyol Derg

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Objective: The pathological effects of matrix metalloproteinases and their tissue inhibitors in cardiovascular diseases are of considerable interest. In our study, we aimed to determine and evaluate the potential significance of circulating matrix metalloproteinases-2 and 9, tissue inhibitors of matrix metalloproteinases-1 and 2 levels in four patient subgroup of pediatric cardiology field and expose pathophysiologic differences between these groups. Methods: Eighty-seven patients with the diagnosis of congenital heart disease and 47 healthy controls were enrolled in the study. The study group was stratified to 4 subgroups; 14 patients with right ventricular volume overload, 30 patients with left ventricular volume overload, 19 patients with left to right shunt who developed pulmonary hypertension and 24 patients with cyanotic congenital heart disease. For evaluation of the relationships between serum matrix metalloproteinases and their tissue inhibitors levels with cardiac structures and functions; complete blood count, arterial oxygen saturation, detailed echocardiographic measurements (including tissue Doppler) in all patients and hemodynamic parameters of the patients who went to cardiac catheterization were recorded. Serum matrix metalloproteinase levels were determined by ELISA test. Statistical evaluations were performed with SPSS 16.0. For parameters showing normal distribution, comparisons were made with t-test and ANOVA test. However, for parameters without normal distribution, groups were compared with Mann-Whitney U test and KruskalWallis test. Results: We demonstrated that serum tissue inhibitors of matrix metalloproteinases-1 levels of patients with pulmonary hypertension secondary to congenital heart diseases were significantly higher than the patients with left to right shunt without pulmonary hypertension and controls (p<0.01). Although serum matrix metalloproteinases and their tissue inhibitors levels in patients with cyanotic congenital heart diseases and patients with right or left ventricular volume overload were found to be altered when compared with controls but not significant. Conclusion: Our data may suggest the possible role of matrix metalloproteinases and their tissue inhibitors on myocardial remodeling in congenital heart defects and especially in patients who developed pulmonary hypertension. (Anadolu Kardiyol Derg 2014; 14: 531-41)

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Treatment with spironolactone for 24 weeks decreases the level of matrix metalloproteinases and improves cardiac function in patients with chronic heart failure of ischemic etiology

Cited by 29 publications

References 17 publications

Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes

Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases levels in pediatric patients with congenital heart disease: Relationship to cardiac functions

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