collagen – ABC CARDIOL

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Editorial

Challenges and Perspectives of Cardiac Fibrosis Biomarkers: From Diagnosis to Clinical Application

Priscila Portugal dos Santos et al. Ricardo Luiz Damatto

As reported by Cheng-Mei et al. myocardial fibrosis is present in various cardiac diseases and can negatively impact the heart. It plays a central role in cardiac dysfunction and failure across different pathologies, serving as a strong predictor of poor clinical outcomes and mortality. However, it is essential to recognize that fibrosis is a complex and heterogeneous process, which can sometimes play a beneficial role, such as after a myocardial infarction. In this context, fibrosis acts as a reparative mechanism, replacing dead cardiomyocytes with scar tissue. This initial fibrotic response is crucial to prevent cardiac rupture, a severe and often fatal complication and one of the leading causes of death in patients with acute myocardial infarction.

Cardiac fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) components, especially collagens, within the myocardium. Understanding this process involves more than just collagen quantity; the characterization of fibrosis also considers collagen quality, the ratio of different fiber types, and the degree of collagen cross-linking. Type I collagen, which predominates in cardiac and vascular ECM, contributes to tissue strength and stiffness due to its thick, dense structure. Type III collagen, being more flexible, aids in ECM compliance. Thus, myocardial elasticity is determined by the ratio of type I to type III collagen fibers.^, Moreover, the degree of covalent cross-linking among the constituent microfibrils is critical to collagen fiber rigidity, increasing their resistance to degradation and significantly contributing to tissue stiffening.^, Therefore, a comprehensive understanding of cardiac fibrosis, aimed at developing new therapies and diagnostic methods, requires evaluating collagen quantity, quality, and cross-linking levels.

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Editorial

The Impact Of Exercise On Inflammation, Oxidative Stress And Remodelling In Cardiac Muscle

Fernando Mendes et al. Diana Martins

Aging is naturally connected with a decline, in some if not all physiological functions, namely loss of bone mass density (BMD) and strength associated with the loss of muscle mass.^–

This muscle loss happens mainly due to an imbalance between muscle protein synthesis and muscle protein breakdown. The increase of catabolic factors such as oxidative stress and inflammation contribute significantly to the above process. Nevertheless, the weakening of strength and muscle loss is not linear, occurring differently in all sexes. Other factors such as a decline in hormonal levels due to menopause phenomenon are thought to be also implicated in this process. In fact, some authors proposed that, in females, an accelerated loss of muscle mass and strength arises at an earlier age than in males, around the time of menopause. A good body of evidence supports that the decline in muscle mass may be in line with the estrogen decrease that typifies menopausal years.

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Original Article

Effects of Physical Training on the Myocardium of Oxariectomized LDLr Knockout Mice: MMP 2/9, Collagen I/III, Inflammation and Oxidative Stress

Ledimar Brianezi et al. Elisabete Ornelas Flávia de Sousa Gehrke Fernando Luiz Affonso Fonseca … Beatriz da Costa Aguiar Alves Luiz Vinicius de Alcantara Sousa Jessica Souza Laura Beatriz Mesiano Maifrino

Abstract

Background:

The emergence of coronary heart disease is increased with menopause, physical inactivity and with dyslipidemia. Physical training is known to promote the improvement of cardiovascular functions.

Objective:

To investigate the effects of aerobic physical training on the left ventricle in ovariectomized LDL knockout mice.

Methods:

Thirty animals were divided into 6 groups (n = 5): Sedentary non-ovariectomized control; Sedentary ovariectomized control; Trained ovariectomized control; Sedentary non-ovariectomized LDL-knockout, sedentary ovariectomized LDL-knockout and trained ovariectomized LDL-knockout. We analyzed the average parameters of apparent density of collagen fibers types I and III, and metalloproteinase type 2 and type 9, were considered significant p < 0.05.

Results:

The results showed that the proposed exercise protocol altered the volume of type I collagen fibers, altered collagen remodeling parameters (MMP-2), and also reduced the 8-hydroxy-2’-deoxyguanosine (8OHdG) oxidative stress parameter.

Conclusion:

Moderate intensity aerobic training acts on collagen fiber volume, on collagen remodeling with the reduction of oxidative stress in the left ventricles of ovariectomized LDL-knockout mice.

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Review Article

Joint hypermobility in patients with mitral valve prolapse

Simone Cavenaghi et al. Lais Helena Carvalho Marino Patrícia Pantaleão Oliveira Neuseli Marino Lamari

Studies on hypermobility have aroused great interest in the last decades, as they are associated to musculoskeletal disorders, as well as abnormalities in several organic systems, such as the mitral valve prolapse. Therefore, in this study, data on the association between joint hypermobility and the mitral valve prolapse were investigated and reviewed. Studies in the literature have shown that genetic alterations in the collagen composition seem to be the main cause of this association.

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Artigo Original

Prognostic value of the collagen volume fraction in hypertrophic cardiomyopathy

Edmundo Arteaga et al. Aloir Queiroz de Araújo Mauricio Bernstein Felix J. A. Ramires … Barbara Maria Ianni Fabio Fernandes Charles Mady

BACKGROUND: In hypertrophic cardiomyopathy (HCM), interstitial myocardial fibrosis is an important histological modification that has been associated with sudden death and evolution toward myocardial dilation. OBJECTIVE:To prospectively evaluate the prognostic value of the collagen volume fraction in HCM. METHODS: An endomyocardial biopsy of the right ventricle was successfully performed in 21 symptomatic patients with HCM. The myocardial collagen volume fraction (CVF) was determined by histology. The CVF was also determined in fragments of nine normal hearts from subjects deceased from non-cardiac causes. The patients were divided into above-median CVF and below-median CVF groups, and their clinical and echocardiographic characteristics and survival curves were compared. RESULTS: Among the patients, the CVF ranged from 1.86% to 29.9%, median 6.19%; in normal hearts, from 0.13% to 1.46%, median 0.61% (p <0.0001 between HCM and control). There were no significant correlations between CVF and baseline echocardiographic measures. Patients with CVF 6.19% were compared and no baseline differences were observed. However, after an average follow-up period of 110 months, four deaths occurred (two sudden, two due to heart failure) in the group with increased CVF, whereas the patients of the group with lower CVF were all alive at the end of the period (p = 0.02). CONCLUSION:For the first time, myocardial fibrosis was prospectively associated with a worse prognosis in patients with HCM. Efforts should be directed to the quantification of myocardial fibrosis in HCM, on the premise that its association with the prognosis can aid in the stratification of risk for defibrillator implantation, and in the prescription of drugs that potentially promote myocardial repair.

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Artigo Original

Correlation of myocardial interstitial collagen in the right ventricular septum with ventricular function of patients with ischemic cardiomyopathy

Marcelo Westerlund Montera et al. Cantídio Drumond Cristina Takiya Cláudio Tinoco Mesquita … Hans Fernando R. Dohmann Charles Mady

BACKGROUND: Myocardial collagen content influences ventricular relaxation, contraction, and morphology. Its relationship with ventricular function in patients (Pts) with ischemic cardiomyopathy (ICMP) has not yet been fully studied in humans. OBJECTIVE: To assess the relationship between interstitial collagen content in non-infarcted areas of the right ventricular septum and ventricular function in ICMP. METHODS: 31 pts with coronary artery disease were divided into four groups as follows:The control group consisted of 7 pts with normal left (LVEF) and right (RVEF) ventricular ejection fraction (group C); Group 1: 5 patients with RVEF < 40%; Group 2: 9 pts with LVEF < 40%; and Group 3, 10 pts with biventricular dysfunction. RVEF and LVEF were measured by radionuclide angiography. For quantitative analysis of interstitial collagen volume fraction (CVF), endomyocardial biopsy specimens were taken from the right ventricle and stained with picrosirius red. RESULTS: Mean CVF was significantly higher in group 3, compared with the control group and with groups 1 and 2 (30.2 ± 7.9% vs. 6.8 ± 3.3% vs. 15.8 ± 4.1% vs. 17.5±7.7%, respectively; p =0.0001). It was also significantly higher in patients belonging to group 2, compared with those in the control group (17.5 ± 7.7% vs. 6.8 ± 3.3%, p =0.0001). CVF was inversely correlated with RVEF (r = – 0.50, p = 0.003) and LVEF (r = -0.70, p = 0.0001). CONCLUSION: In ICMP, CVF is elevated in non-infarcted areas of the right ventricular septum and inversely correlated with right and left ventricular function.

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Artigo Original

The role of storage of interstitial myocardial collagen on the overlife rate of patients with idiopathic and chagasic dilated cardiomyopathy

Vera Lopes Nunes et al. Felix José Alvarez Ramires Walace de Souza Pimentel Fábio Fernandes … Barbara Maria Ianni Charles Mady

OBJECTIVE: To find out whether there is a correlation between a myocardial structural marker and the overlife rate of patients with dilated cardiomyopathy. METHODS: Using endomyocardial biopsy and 2D-echocardiogram, we studied nine patients with no changes in myocardial structure (control) and 45 patients with severe dilated cardiomyopathy of idiopathic etiology (IDCM) and of Chagasic etiology (CDCM). We analyzed the correlation between the quantity of interstitial myocardial collagen (ICVF) and the overlife rates of these patients. We also evaluated the difference in ICVF between these groups and whether fibrosis interfered on the geometry and function of the myocardium. RESULTS: We observed that ICVF was 15 times higher in cardiomyopathy patients than in the control group, but there was no difference in ICVF between CDCM and IDCM (*p < 0.001) patients. There was no correlation between ICVF and the overlife rate in cardiomyopathy patients (IDCM p = 0.249, and CDCM p = 0.587). We observed a significant correlation between ICVF and left ventricular ejection fraction (LVEF) only for IDCM. There was no correlation between ICVF and left ventricular diastolic diameter in either etiology. CONCLUSION: There was no difference in myocardial fibrosis between patients with CDCM or IDCM, and there was no correlation between fibrosis and the prognosis either for IDCM or CDCM. There was a correlation between myocardial fibrosis and LVEF only for IDCM.

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Artigo Original

Myocardial remodeling in chronic pressure or volume overload in the rat heart

Luiz Shiguero Matsubara et al. Silvia Narikawa Ana Lucia dos Anjos Ferreira Sergio Alberto Rupp de Paiva … Leonardo Mamede Zornoff Beatriz Bojikian Matsubara

OBJECTIVE: To compare cardiac structural changes in experimental pressure and volume overload models. METHODS: The study analysis included renovascular hypertensive rats (RVH, n=8), normotensive rats with volume overload caused by an aortocaval fistula (ACF, n=10) and control rats (CONT, n=8). After four weeks, tail cuff blood pressure (SBP) was recorded. Rats were killed, the hearts were excised and the right and left ventricles (RV&LV) were weighed (RVW&LVW). Using histological sections, myocyte cross sectional areas (MA). LV wall thickness (LVWT) LV cavity diameter (LVD), normalized LVWT (LVWT/LVD) and collagen volume fraction (CVF) were measured. The comparisons were made using the ANOVA and Tukey test for a significance level of 5%. RESULTS: Tail cuff blood pressure (mmHg) was higher in the RVH group (RVH = 187 ± 22; CONT = 125 ± 10; ACF = 122 ± 6, p<0.05). LV hypertrophy was observed in the RVH and ACF groups. The ACF group presented a significant increase in size of LVD, compared to CONT and RVH. The absolute and normalized ventricular wall thickness were similar among the groups. The RVH group presented a significant increase in CVF compared to CONT group and ACF group. CONCLUSION: Cardiac remodeling patterns following volume or pressure overload are distinct, suggesting that their implications on ventricular dysfunction are not interchangeable.

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