An Investigation of Fibulin-2 in Hypertrophic Cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart muscle disease, with a prevalence of at least 1 in 500 in the general population. The disease is pleiotropic and is characterized by an increased stiffness of the myocardium, partly due to changes in the extracellular matrix (ECM), with elevated levels of interstitial fibrosis. Myocardial fibrosis is linked to impaired diastolic function and possibly phenotypic heterogeneity of HCM. The ECM consists of a very large number of proteins, which actively interact with each other as well as with myocardial cells. The role of other multiple components of the ECM in HCM has not been defined. Fibulin-2 is a glycoprotein component of the ECM, which plays an important role during embryogenesis of the heart; however, its role in adult myocardium has not been adequately studied. We here describe, for the first time, abnormal expression of fibulin-2 in the myocardium in patients with HCM as compared to normal controls. This abnormal expression was localized in the cytoplasm of myocardial cells and in the interstitial fibroblasts. In addition, fibulin-2 levels, measured by ELISA, were significantly elevated in the serum of patients with HCM as compared to normal controls.

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

“…Signaling pathways include cytokine signaling in immune system [48], extracellular matrix organization [49], diseases of metabolism [50], hemostasis [51], innate immune system [52], metabolism of lipids [53] [87], CES1 [88], CYP19A1 [89], PLAC8 [90], CD36 [91], GIPR (gastric inhibitory polypeptide receptor) [92], ARG1 [93], MSR1 [94], DOCK2 [95], S1PR1 [96], OXTR (oxytocin receptor) [97], F11R [98], LEPR (leptin receptor) [99], AR (androgen receptor) [100], DKK3 [101], FOXO1 [102], PIK3CB [103], WWP1 [104], PHIP (pleckstrin homology domain interacting protein) [105], MPZL3 [106], FBXO2 [107], GUCY2C [108], ADRA2A [109], CHRNA5 [110], GLP2R [111], SDC3 [112], NFAT5 [113], PON2 [114], PRNP (prion protein) [115], DGKE (diacylglycerol kinase epsilon) [116], ARHGAP21 [117], COQ2 [118], EPHX2 [119] and FAM3C [120] were observed to be associated with the progression of obesity. Vargas-Alarcón et al [ [133], Jiang et al [134], Yu et al [135], Jiang et al [136], Huang et al [137], Scuruchi et al [138], Wang et al [139], Ibrahim et al [140], Zha et al …”

Identification of Key Modules and Hub Genes in Hypertrophic Cardiomyopathy Based on Integrative Weighted Gene Co-expression Network Analysis

“…Previous studies have well demonstrated that excessive accumulation of ECM impaired cardiac contractile function and emphasized the role of myocardial brosis in the morphogenesis and establishment of HCM (32,33). Abnormal expression of ECM components like Fibulin-2 and TXNDC5 might augment detrimental interactions in HCM (34,35) and HCM-related matrix undermined healthy cardiomyocytes with prolonged contractions and poor relaxation (36). Additionally, TGF-beta signaling pathway, which is relatively negative enriched in TUBA3D, participates in pathogenesis and development of HCM.…”

Structural and Functional Characterization of the Aorta in Hypertrophic Obstructive Cardiomyopathy

“…Thoracic aortic biopsies were collected, processed and prepared for staining as described before 25 . Briefly, for fibrous collagen staining, slides were incubated in picrosirius red stain (Abcam) for 1 hr and washed in 0.5% acetic acid for differentiation.…”

“…Section preparation was performed as described before 25,26 . All antibodies were diluted using blocking solution; α-SMA 1:300 (Thermo Scientific™, # MS- Rabbit IgG H&L Alexa Fluor® 488) (Abcam, #ab150077) at a 1:500 dilution, incubated in the dark for 1 hr at RT, and then mounted with DAPI-containing mounting media (Invitrogen™, Carlsbad, CA, USA, #P36962).…”

“…Tissue biopsies were lysed and prepared for separation as described before 25,28 . Briefly, 5 μg of protein per sample was separated and then transferred from the SDS polyacrylamide gel onto Whatman® Protran® Nitrocellulose Transfer Membrane (0.2 μm) (Sigma) using a Biorad transfer module, protein transfer buffer (1X NuPage transfer buffer, 10% methanol in dH2O).…”