Article

The extracellular matrix: at the center of it all.

Texas A&M Health Science Center College of Medicine, Division of Molecular Cardiology, 1901 South 1st Street, Building 205, Room 1R24, Temple, TX 76504, USA.
Journal of Molecular and Cellular Cardiology (Impact Factor: 5.15). 09/2009; 48(3):474-82. DOI: 10.1016/j.yjmcc.2009.08.024
Source: PubMed

ABSTRACT The extracellular matrix is not only a scaffold that provides support for cells, but it is also involved in cell-cell interactions, proliferation and migration. The intricate relationships among the cellular and acellular components of the heart drive proper heart development, homeostasis and recovery following pathological injury. Cardiac myocytes, fibroblasts and endothelial cells differentially express and respond to particular extracellular matrix factors that contribute to cell communication and overall cardiac function. In addition, turnover and synthesis of ECM components play an important role in cardiac function. Therefore, a better understanding of these factors and their regulation would lend insight into cardiac development and pathology, and would open doors to novel targeted pharmacologic therapies. This review highlights the importance of contributions of particular cardiac cell populations and extracellular matrix factors that are critical to the development and regulation of heart function.

0 Bookmarks
 · 
84 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Galectin-3 is involved in fibrosis and inflammation and plays a role in heart failure, renal disease, obesity and cancer. We aimed to establish the relationship between galectin-3 and cardiovascular (CV) risk factors and mortality in the general population. This study included 7968 subjects from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, with a median follow-up of approximately 10 years. Plasma galectin-3 was measured in baseline samples. We investigated the relationships between galectin-3 levels, demographic characteristics and risk factors of CV disease. We determined the prognostic value for all-cause, CV and cancer mortality. The mean age of the population was 50 ± 13 years. Mean blood pressure was 129/74 mmHg, mean cholesterol was 5.7 ± 1.1 mmol L(-1) and median galectin-3 was 10.9 ng mL(-1) [interquartile range (IQR) 9.0-13.1]. Galectin-3 levels correlated with a wide range of risk factors of CV disease, including blood pressure, serum lipids, body mass index, renal function and N-terminal pro-B-type natriuretic peptide (P < 0.0001). We observed a strong association between galectin-3 and age. Furthermore, we found a gender interaction, with female subjects (n = 4001) having higher median galectin-3 levels (11.0 ng mL(-1) , IQR 9.1-13.4 vs. men (n = 3967) 10.7 ng mL(-1) , IQR 8.9-12.8; P < 0.0001), and galectin-3 levels in women more strongly correlated with risk factors of CV disease. After correction for the classical CV risk factors (smoking, blood pressure, cholesterol and diabetes), galectin-3 levels independently predicted all-cause mortality (hazard ratio per SD galectin-3 1.09, 95% CI 1.01-1.19; P = 0.036), but not CV and cancer mortality separately. Galectin-3 is associated with age and risk factors of CV disease, with a strong gender interaction for these correlations. Galectin-3 predicts all-cause mortality in the general population.
    Journal of Internal Medicine 10/2011; 272(1):55-64. · 6.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Collagen XIV is a fibril-associated collagen with an interrupted triple helix (FACIT). Previous studies have shown that this collagen type regulates early stages of fibrillogenesis in connective tissues of high mechanical demand. Mice null for Collagen XIV are viable, however formation of the interstitial collagen network is defective in tendons and skin leading to reduced biomechanical function. The assembly of a tightly regulated collagen network is also required in the heart, not only for structural support but also for controlling cellular processes. Collagen XIV is highly expressed in the embryonic heart, notably within the cardiac interstitium of the developing myocardium, however its role has not been elucidated. To test this, we examined cardiac phenotypes in embryonic and adult mice devoid of Collagen XIV. From as early as E11.5, Col14a1(-/-) mice exhibit significant perturbations in mRNA levels of many other collagen types and remodeling enzymes (MMPs, TIMPs) within the ventricular myocardium. By post natal stages, collagen fibril organization is in disarray and the adult heart displays defects in ventricular morphogenesis. In addition to the extracellular matrix, Col14a1(-/-) mice exhibit increased cardiomyocyte proliferation at post natal, but not E11.5 stages, leading to increased cell number, yet cell size is decreased by 3months of age. In contrast to myocytes, the number of cardiac fibroblasts is reduced after birth associated with increased apoptosis. As a result of these molecular and cellular changes during embryonic development and post natal maturation, cardiac function is diminished in Col14a1(-/-) mice from 3months of age; associated with dilation in the absence of hypertrophy, and reduced ejection fraction. Further, Col14a1 deficiency leads to a greater increase in left ventricular wall thickening in response to pathological pressure overload compared to wild type animals. Collectively, these studies identify a new role for type XIV collagen in the formation of the cardiac interstitium during embryonic development, and highlight the importance of the collagen network for myocardial cell survival, and function of the working myocardium after birth.
    Journal of Molecular and Cellular Cardiology 08/2012; 53(5):626-38. · 5.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the regulation of the proteins ADAM-15 and ADAM-17 in intrauterine adhesions (IUA). 68 patients were found to have IUA in a study performed at our Department of Gynecology, and 18 control volunteer participants were recruited in the study. The patients with IUA were assigned to three groups according to the classification of March et al.: IUA-I (n=28), IUA-II (n=22), and IUA-III (n=18). All the volunteers were assigned to the control group (Con, n=18). The expression of ADAM-15 and ADAM-17 in the adhesive band tissue in patients and the endometrium in volunteers was detected by western blot, real-time PCR, and immunohistochemistry. The expression of ADAM-15 and ADAM-17 was significantly upregulated in both protein level and transcript level in IUA patients compared to that in controls. ADAM-15 expression was significantly higher in IUA-III (4.59±0.15) compared to IUA-II (3.18±0.12) and IUA-I (2.11±0.17; P<0.01). ADAM-17 expression was also significantly higher in IUA-III (3.25±0.11) compared to IUA-II (2.21±0.15) and IUA-I (1.78±0.21; P<0.01). The transcript levels of ADAM-15 and ADAM-17 showed similar patterns, and were markedly higher in grade III IUA patients compared to grade II and grade I. The severity of IUA was positively correlated to the protein and transcript expression level of ADAM-15 and ADAM-17 in uterine tissue. The development of IUA is associated with regulation of ADAM15 and ADAM-17, which may be potential biological markers for evaluating the severity of intrauterine adhesions.
    European journal of obstetrics, gynecology, and reproductive biology 08/2013; · 1.97 Impact Factor

Full-text (2 Sources)

View
27 Downloads
Available from
May 26, 2014