Fibro-adipose substitution has a double detrimental effect on the myocardium in arrhythmogenic cardiomyopathy (ACM), worsening arrhythmogenesis by creating a non-conductive substrate, and causing ventricular dysfunction leading to heart failure. Notably, to-date no etiological therapy is available. This work introduces, for the first time, the stromal cardiac compartment as a key player in ACM ventricular adipose substitution: we demonstrated that cardiac human mesenchymal stromal cells undergo adipogenic differentiation both in ACM explanted hearts and in culture through a PKP2-dependent mechanism. Cardiac mesenchymal stromal cells constitute a suitable cellular platform for future mechanistic studies and a potential target for future therapies.
Sequence heterogeneity of hepatitis C virus (HCV) is unevenly distributed along the genome, and maximal variation is confined to a short sequence of the HCV second envelope glycoprotein (E2), designated hypervariable region 1 (HVR1), whose biological function is still undefined. We prospectively studied serological responses to synthetic oligopeptides derived from HVR1 sequences of patients with acute and chronic HCV infection obtained at baseline and after a defined follow-up period. Extensive serological cross-reactivity for unrelated HVR1 peptides was observed in the majority of the patients. Antibody response was restricted to the IgG1 isotype and was focused on the carboxyterminal end of the HVR1 region. Cross-reactive antibodies could be readily elicited following immunization of mice with multiple antigenic peptides carrying HVR1 sequences derived from our patients. The vigor and heterogeneity of cross-reactive antibody responses were significantly higher in patients with chronic hepatitis compared with those with acute hepatitis and in patients infected with HCV type 2 compared with patients infected with other viral genotypes (predominantly type 1), which suggest that higher time-related HVR1 sequence diversification previously described for type 2 may result from immune selection. The finding of a statistically significant correlation between HVR1 sequence variation, and intensity, and crossreactivity of humoral immune responses provided stronger evidence in support of the contention that HCV variant selection is driven by the host's immune pressure. (HEPATOL-OGY 1999;30:537-545.)Hepatitis C virus (HCV) causes chronic infection in more than 60% of exposed individuals through pathogenetic mechanisms that are still poorly understood. 1 Similarly to human immunodeficiency virus (HIV), HCV is able to persist for a virtually indefinite period of time in the host, despite the coexistence of virus-specific immune responses. 2 How HCV induces chronic infection in the face of detectable cellular and humoral immune responses is currently unknown, but the ability of the virus to undergo rapid and substantial sequence modifications is thought to be a major factor in this process. [2][3][4][5][6][7][8][9][10][11] Sequence variation is unevenly distributed along the HCV genome with maximal nucleotide and aminoacid replacements being localized in a stretch of 31 residues at the N-terminus of the second envelope glycoprotein (E2) region named hypervariable region 1 (HVR1). 12 Sequential studies of sequence changes in acute and chronic HCV infection have shown that viral variants are continuously being selected in this region 13,14 and, therefore, HVR1 variation may be a mechanism by which HCV evades neutralizing responses, leading to persistent infection.Most studies point to HVR1 as the major immunogenic domain of E2, although the presence of additional B-cell sites outside HVR1 has been documented, 15 and a conserved B-cell epitope, only partially overlapping with HVR1, has been recently described that competes for ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.