Proteomic analysis of human plasma in chronic rheumatic mitral stenosis reveals proteins involved in the complement and coagulation cascade

BACKGROUND: Rheumatic fever in childhood is the most common cause of Mitral Stenosis in developing countries. The disease is characterized by damaged and deformed mitral valves predisposing them to scarring and narrowing (stenosis) that results in left atrial hypertrophy followed by heart failure. Presently, echocardiography is the main imaging technique used to diagnose Mitral Stenosis. Despite the high prevalence and increased morbidity, no biochemical indicators are available for prediction, diagnosis and management of the disease. Adopting a proteomic approach to study Rheumatic Mitral Stenosis may therefore throw some light in this direction. In our study, we undertook plasma proteomics of human subjects suffering from Rheumatic Mitral Stenosis (n = 6) and Control subjects (n = 6). Six plasma samples, three each from the control and patient groups were pooled and subjected to low abundance protein enrichment. Pooled plasma samples (crude and equalized) were then subjected to in-solution trypsin digestion separately. Digests were analyzed using nano LC-MS(E). Data was acquired with the Protein Lynx Global Server v2.5.2 software and searches made against reviewed Homo sapiens database (UniProtKB) for protein identification. Label-free protein quantification was performed in crude plasma only. RESULTS: A total of 130 proteins spanning 9–192 kDa were identified. Of these 83 proteins were common to both groups and 34 were differentially regulated. Functional annotation of overlapping and differential proteins revealed that more than 50% proteins are involved in inflammation and immune response. This was corroborated by findings from pathway analysis and histopathological studies on excised tissue sections of stenotic mitral valves. Verification of selected protein candidates by immunotechniques in crude plasma corroborated our findings from label-free protein quantification. CONCLUSIONS: We propose that this protein profile of blood plasma, or any of the individual proteins, could serve as a focal point for future mechanistic studies on Mitral Stenosis. In addition, some of the proteins associated with this disorder may be candidate biomarkers for disease diagnosis and prognosis. Our findings might help to enrich existing knowledge on the molecular mechanisms involved in Mitral Stenosis and improve the current diagnostic tools in the long run. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1559-0275-11-35) contains supplementary material, which is available to authorized users

Identification Of Proteins Or Peptides For Development Of Biomarkers Of Heart Diseases

Heart disease is one of the foremost reasons behind mortality and morbidity globally. It is a major economic burden especially in low and middle-income countries (LMICs). Different types of cardiovascular diseases may occur in the heart or blood vessels. Functionally, heart disease is the difficulty of the heart to pump sufficient blood to meet the metabolic needs of the body. It can occur quickly as with an AMI or progress gradually over years as with chronic HF. In each case, the heart is unable to efficiently or effectively contract making it more difficult to maintain cardiac output.Mortality resulting from cardiovascular diseases stood at about 17.1 million in 2004, representing 29% of all global deaths, and as estimated by WHO, about 23.6 million individuals will die each year from cardiovascular diseases by 2030. Hence, primary and secondary prevention of CVD are public health priorities (1). To prevent and control cardiovascular diseases, significant efforts have been made to understand the pathogenesis of such diseases. Generally, these diseases result from the crosstalk between lifestyle risk factors, environmental cues and the inherent intracellular system. Therefore, the pathogenesis of cardiovascular diseases is complicated (2)

Circulating Carboxy-Terminal Propeptide of type I Procollagen is Increased in Rheumatic Heart Disease

Mitral valve is mostly affected in rheumatic heart disease which is prevalent in developing countries [1–3] and thousands of new cases are being diagnosed worldwide every year [1–3]. It is known that extensive fibrosis occurs in the rheumatic valve [4]. Serum carboxyterminal propeptide of type I procollagen (PICP), the marker of collagen synthesis was reported as a marker of extracellular matrix (ECM) remodelling in various heart diseases [5–8]. We therefore, measured the levels of circulating PICP to explore the severity of ECM remodelling in rheumatic heart disease

Induction of apoptosis by zerumbone isolated from Zingiber zerumbet (L.) Smith in protozoan parasite Leishmania donovani due to oxidative stress

In the present context of emergence of resistance aligned with the conventional anti-leishmanial drugs and occasional treatment failure compelled us to continue the search for replaceable therapeutic leads against Leishmania infection. Various ginger spices of the Zingiberaceae family are widely used as spices, flavouring agents, and medicines in Southeast Asia because of their unique flavour as well as due to their medicinal properties. Zerumbone, a natural component of Zingiber zerumbet (L.) Smith, has been studied for its pharmacological potential as antiulcer, antioxidant, anticancer, and antimicrobial. In this study, we have shown that zerumbone could induce ROS mediated apoptosis in Leishmania donovani promastigotes and also found effective in reducing intracellular amastigotes in infected-macrophages. We emphasized the potential of zerumbone to be employed in the development of new therapeutic drugs against L. donovani infection and provided the basis for future research on the application of transitional medicinal plants. Keywords: Leishmania donovani, Zingiber zerumbet, Zerumbone, Anti-leishmanial, RO

Overall Performance of Different Parameters According to ROC Curves for Prediction of RHD.

<p>p <0.05 considered significantly different.</p><p>AUC, area under curve; CI, confidence interval; LR, likelihood ratio; MMP-1, matrix metalloproteinase -1; NPV, negative predictive value; PICP, carboxy terminal propeptide of type I collagen; PIIINP, amino terminal propeptide of type III collagen; PPV, positive predictive value; TIMP-1, tissue inhibitor of matrix metalloproteinase-1.</p

Histopathology of heart valve.

<p>(A) Representative images (100× magnification) of hematoxylin-eosin stained sections of 1 normal heart valve (control) and 3 rheumatic valve samples (RHD). Rheumatic mitral valve tissue section shows abundance of inflammatory cells (arrow head), fibrosis (blue arrow) and neovascularisation (black arrow). Normal mitral valve section shows wavy arrangement of collagen fibres (black arrow). Scale bar represents 50 µm. (B) Representative images (100×) of Masson's trichrome stained cross sections showing dense collagen deposition (arrow) in mitral valve tissue of RHD patient compared to loose parallel pattern of collagen (arrow) in normal heart valve. Scale bar represents 50 µM.</p

Receiver operating characteristics curve for biomarkers in rheumatic heart disease subjects.

<p>Receiver operating characteristics curve for biomarkers in rheumatic heart disease subjects.</p

Overall Performance of Different Parameters According to ROC Curves for Prediction of Mitral Stenosis.

<p>p<0.05 considered significantly different.</p><p>AUC, area under curve; CI, confidence interval; LR, likelihood ratio; MMP-1, matrix metalloproteinase -1; NPV, negative predictive value; PICP, carboxy terminal propeptide of type I collagen; PIIINP, amino terminal propeptide of type III collagen; PPV, positive predictive value; TIMP-1, tissue inhibitor of matrix metalloproteinase-1.</p

Plasma concentrations of circulating biomarkers of collagen turnover in normal, MS and MR subjects.

<p>(A) Mean plasma PICP in control, MS and MR subjects before (Pre Op) valve replacement surgery. (B) Progressive reduction in plasma PICP concentration one month and one year or above following mitral valve replacement. (C) Mean plasma PIIINP in control, MS and MR subjects before (Pre Op) valve replacement surgery. (D) Progressive decrease in plasma PIIINP concentration one month and one year or more after mitral valve replacement. (E) Mean plasma concentration of total MMP-1 in control, MS and MR subjects. (F) Mean TIMP-1 concentration in control, MS and MR subjects. (G) Plasma MMP-1/TIMP-1 ratio in control, MS and MR subjects.</p