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Proteomic analysis of mitral valve in Lewis rat with acute rheumatic heart disease.

ABSTRACT: Rheumatic heart disease (RHD) makes a heavy burden in human lives and economy. The proteomic analysis of acute rheumatic heart disease (ARHD) can provide precious data to study RHD at the early stages, but no one has looked into. So based on our early research we applied the method of continuous GAS stimulation on Lewis rats to duplicate the animal model of ARHD. And the mitral valves of rats in control group (n=10) and ARHD group (n=10) were selected for proteomic analysis of ARHD with the iTRAQ labeling based 2D LC-ESI-MS/MS quantitative technology. We identified 3931 proteins in valve tissue out of which we obtained 395 differentially expressed proteins containing 176 up-regulated proteins and 119 down-regulated proteins. Changes in levels of GAPDH (6.793 times higher than the control group) and CD9 (2.63 times higher than the control group) were confirmed by Western blot or immunohistochemistry. The differentially expressed proteins such as GAPDH, CD9, myosin, collagen and RAC1 may be potential biomarkers for ARHD. Moreover, the mitral valve protein profile shed light on further understanding and investigating ARHD.

SUBMITTER: Li W

PROVIDER: S-EPMC4713514 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Proteomic analysis of mitral valve in Lewis rat with acute rheumatic heart disease.

Li Wenting W Zeng Zhiyu Z Gui Chun C Zheng Huilei H Huang Weiqiang W Wei Heng H Gong Danping D

International journal of clinical and experimental pathology 20151101 11

Rheumatic heart disease (RHD) makes a heavy burden in human lives and economy. The proteomic analysis of acute rheumatic heart disease (ARHD) can provide precious data to study RHD at the early stages, but no one has looked into. So based on our early research we applied the method of continuous GAS stimulation on Lewis rats to duplicate the animal model of ARHD. And the mitral valves of rats in control group (n=10) and ARHD group (n=10) were selected for proteomic analysis of ARHD with the iTRA ...[more]

PMID: 26823728

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Project description:BackgroundThe clinical outcome of mitral valve repair (MVP) is considerably more favorable than that of mitral valve replacement (MVR) in patients with degenerative mitral disease. However, rheumatic heart disease (RHD) is still the predominant cause of mitral valve surgery in developing countries and the advantages of MVP in RHD have still not been definitely proven. The aim of this meta-analysis was thus to evaluate the suitability of MVP in patients with RHD. Considering the difference between mechanical and biological valves, we distinguished them from each other and compared them with MVP individually.MethodsA comparison of clinical outcomes of MVP and MVR in patients with RHD was performed based on clinical trial data. Relevant articles published from January 1, 1990 until March 1, 2020 were identified in Pubmed, Cochrane Library, and China National Knowledge Infrastructure database (CNKI). Studies that lacked direct comparisons between MVP and MVR were excluded.ResultsA total of 16 studies with 8659 patients were included in the analysis. The MVP group displayed lower early and long-term mortality, and fewer valve-related events and major adverse events. However, this patient group required more reoperations compared with the MVR group. Similar results were observed after distinguishing between mechanical and bioprosthetic valves to compare MVP with MVR (mech-valves), but no statistically significant difference was identified in the reoperation rate between MVP and MVR (bio-valves). MVP was further associated with increased risk of mitral reoperation in patients undergoing concomitant aortic valve replacement (AVR) surgery but without any improved early and long-term survival.ConclusionsMVP and MVR are beneficial for patients with RHD. For skilled surgeons, MVP can be performed for some suitable patients with RHD and is preferred for elderly patients or patients with contraindications of anticoagulation. However, MVR is more appropriate when concomitant AVR is needed.

Project description:BackgroundRheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. It is a major public health concern in developing countries. In RHD, mostly the valves get affected. The present study investigated whether extracellular matrix remodelling in rheumatic valve leads to altered levels of collagen metabolism markers and if such markers can be clinically used to diagnose or monitor disease progression.MethodologyThis is a case control study comprising 118 subjects. It included 77 cases and 41 healthy controls. Cases were classified into two groups- Mitral Stenosis (MS) and Mitral Regurgitation (MR). Carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), total Matrix Metalloproteinase-1(MMP-1) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) were assessed. Histopathology studies were performed on excised mitral valve leaflets. A p value <0.05 was considered statistically significant.ResultsPlasma PICP and PIIINP concentrations increased significantly (p<0.01) in MS and MR subjects compared to controls but decreased gradually over a one year period post mitral valve replacement (p<0.05). In MS, PICP level and MMP-1/TIMP-1 ratio strongly correlated with mitral valve area (r?=?-0.40; r?=?0.49 respectively) and pulmonary artery systolic pressure (r?=?0.49; r?=?-0.49 respectively); while in MR they correlated with left ventricular internal diastolic (r?=?0.68; r?=?-0.48 respectively) and systolic diameters (r?=?0.65; r?=?-0.55 respectively). Receiver operating characteristic curve analysis established PICP as a better marker (AUC?=?0.95; 95% CI?=?0.91-0.99; p<0.0001). A cut-off >459 ng/mL for PICP provided 91% sensitivity, 90% specificity and a likelihood ratio of 9 in diagnosing RHD. Histopathology analysis revealed inflammation, scarring, neovascularisation and extensive leaflet fibrosis in diseased mitral valve.ConclusionsLevels of collagen metabolism markers correlated with echocardiographic parameters for RHD diagnosis.

Project description:Background: Bioprosthetic heart valve has limited durability and lower long-term performance especially in rheumatic heart disease (RHD) patients that are often subject to multiple redo operations. Minimally invasive procedures, such as transcatheter valve-in-valve (ViV) implantation, may offer an attractive alternative, although data is lacking. The aim of this study was to evaluate the baseline characteristics and clinical outcomes in rheumatic vs. non-rheumatic patients undergoing ViV procedures for severe bioprosthetic valve dysfunction. Methods: Single center, prospective study, including consecutive patients undergoing transcatheter ViV implantation in aortic, mitral and tricuspid position, from May 2015 to September 2020. RHD was defined according to clinical history, previous echocardiographic and surgical findings. Results: Among 106 patients included, 69 had rheumatic etiology and 37 were non-rheumatic. Rheumatic patients had higher incidence of female sex (73.9 vs. 43.2%, respectively; p = 0.004), atrial fibrillation (82.6 vs. 45.9%, respectively; p < 0.001), and 2 or more prior surgeries (68.1 vs. 32.4%, respectively; p = 0.001). Although, device success was similar between groups (75.4 vs. 89.2% in rheumatic vs. non-rheumatic, respectively; p = 0.148), there was a trend toward higher 30-day mortality rates in the rheumatic patients (21.7 vs. 5.4%, respectively; p = 0.057). Still, at median follow-up of 20.7 [5.1-30.4] months, cumulative mortality was similar between both groups (p = 0.779). Conclusion: Transcatheter ViV implantation is an acceptable alternative to redo operations in the treatment of patients with RHD and severe bioprosthetic valve dysfunction. Despite similar device success rates, rheumatic patients present higher 30-day mortality rates with good mid-term clinical outcomes. Future studies with a larger number of patients and follow-up are still warranted, to firmly conclude on the role transcatheter ViV procedures in the RHD population.

Dataset Information

Proteomic analysis of mitral valve in Lewis rat with acute rheumatic heart disease.

Publications

Proteomic analysis of mitral valve in Lewis rat with acute rheumatic heart disease.

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