Cardiac isoform of alpha-2 macroglobulin as a novel diagnostic marker for cardiac diseases

Rathinavel, Andiappan; Dhandapany, Perundurai S.; Annapoorani, Ponnambalam; Ramasamy, Subbiah; Selvam, Govindan Sadasivam

doi:10.1097/01.hjr.0000176513.07037.83

Cited by 11 publications

(5 citation statements)

References 9 publications

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“…Earlier studies showed that cardiac isoform of alpha 2 macroglobulin (CA2M), is a high molecular weight serum protein (182000Mr), involved in development of cardiac hypertrophy in rats [5]. Further, our studies confirmed that CA2M could be used as a diagnostic marker for cardiac disease [6], cardiac manifestations in HIV/AIDS and diabetic patients [7,8]. Since it is a novel area of research, further studies are required to confirm the clinical utility of CA2M in HIV patients.…”

Section: Introductionsupporting

confidence: 85%

Cardiac Isoform of Alpha 2 Macroglobulin and Its Reliability as a Cardiac Marker in HIV Patients

Ramasamy

Chengat

Clifton

et al. 2010

Heart, Lung and Circulation

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Section: Introductionsupporting

confidence: 85%

Cardiac Isoform of Alpha 2 Macroglobulin and Its Reliability as a Cardiac Marker in HIV Patients

Ramasamy

Chengat

Clifton

et al. 2010

Heart, Lung and Circulation

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“…Although acute phase proteins including α 2 M [46] have been established as markers of cardiac disease and dysfunction, nearly nothing is known about their function in adaptive responses to cardiac insults like cardiac hypertrophy or cardiac infarction. Systemic administration of rapamycin has been used successfully for the treatment of transplant rejection in clinical practice, and it has therefore been suggested to be a useful therapeutic means to suppress cardiac hypertrophy in patients [44].…”

Section: Discussionmentioning

confidence: 99%

The acute phase protein α2-macroglobulin induces rat ventricular cardiomyocyte hypertrophy via ERK1,2 and PI3-kinase/Akt pathways☆

Padmasekar

Nandigama

Wartenberg

et al. 2007

Cardiovascular Research

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Objective: α 2 -macroglobulin (α 2 M) is an acute phase protein released to the serum upon challenges such as cardiac hypertrophy and infarction. Here we report on the role of α 2 M in the induction of hypertrophic cell growth, contractile responsiveness of rat ventricular cardiomyocytes, and on the underlying extracellular regulated kinase 1,2 (ERK1,2) and phosphoinositide 3-kinase (PI3-kinase)/Akt pathways. Methods: Cell volume and cross-sectional areas were assessed as parameters of hypertrophic growth, and real time RT-PCR for the analysis of hypertrophy-related genes was performed. Protein synthesis was analyzed by 14 C-phenylalanine incorporation. Activation of ERK1,2, PI3-kinase and Akt was assessed by immunohistochemical analysis of phosphorylated proteins. Contractile responsiveness was investigated by determination of cell shortening following electrical field stimulation. Intracellular calcium concentration [Ca 2+ ] i was determined by fluo-3 microfluorometry. Results: Treatment of ventricular cardiomyocytes for 24 h with α 2 M significantly increased cell volume and protein synthesis as well as expression of hypertrophy-associated genes [brain natriuretic protein (BNP), β-myosin heavy chain (β-MHC), myosin light chain-2 (MLC-2), atrial natriuretic factor (ANF), and skeletal α-actin]. Comparable effects were achieved by treatment of cells with an antibody directed against the α 2 M-receptor LDL receptor-related protein-1 (LRP-1) and counteracted upon coincubation with receptor-associated protein (RAP), suggesting an involvement of α 2 M-LRP-1 signalling. Furthermore, α 2 M treatment increased sarcoplasmic reticulum Ca 2+ -ATPase (SERCA2a) expression, diastolic and systolic [Ca 2+ ] i , and contractile responsiveness after electrical stimulation. Shortly after α 2 M stimulation, activation of ERK1,2, Akt, and PI3-kinase pathways was observed. Consequently, α 2 M-induced protein synthesis was inhibited upon treatment with the ERK1,2 inhibitor UO126 as well as by LY294002 and wortmannin, which inhibit PI3-kinase, and by rapamycin, which inhibits mammalian target of rapamycin (mTOR) downstream of Akt. Conclusions: Our data show that α 2 M induces hypertrophic cell growth in rat ventricular cardiomyocytes via ERK1,2 and PI3-kinase/Akt and improves cardiac cell function.

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“…In addition to this, gelsolin has been identified as being down-regulated by gel electrophoresis followed by MALDI-TOF/MS and tandem mass spectrometry. Alpha-2-macroglobulin, a protease inhibitor, has been associated with the progression of cardiac disease87. Peptidase inhibitor 16 (PI16), Ig mu heavy chain disease protein, and thyroid receptor-interacting protein 11, were not readily identified through literature searches as having a known role in cardiovascular disease.…”

Section: Resultsmentioning

confidence: 99%

Effects of Lead and Mercury on the Blood Proteome of Children

et al. 2010

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Heavy metal exposure in children has been associated with a variety of physiological and neurological problems. The goal of this study was to utilize proteomics to enhance the understanding of biochemical interactions responsible for the health problems related to lead and mercury exposure at concentrations well below CDC guidelines. Blood plasma and serum samples from 34 children were depleted of their most abundant proteins using antibody-based affinity columns and analyzed using two different methods, LC-MS/MS and 2-D electrophoresis coupled with MALDI-TOF/MS and tandem mass spectrometry. Apolipoprotein E demonstrated an inverse significant association with lead concentrations (average being one microgram/deciliter) as deduced from LC-MS/MS and 2-D electrophoresis and confirmed by Western blot analysis. This coincides with prior findings that Apolipoprotein E genotype moderates neurobehavioral effects in individuals exposed to lead. Fifteen other proteins were identified by LC-MS/MS as proteins of interest exhibiting expressional differences in the presence of environmental lead and mercury.

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Cardiac isoform of alpha-2 macroglobulin as a novel diagnostic marker for cardiac diseases

Abstract: Levels of CA2M in cardiac diseases were significantly higher than other sample groups but moderately elevated in leprosy. This protein could be considered for diagnosis of cardiac diseases as a serum marker.

Cited by 11 publications

References 9 publications

Cardiac Isoform of Alpha 2 Macroglobulin and Its Reliability as a Cardiac Marker in HIV Patients

Cardiac Isoform of Alpha 2 Macroglobulin and Its Reliability as a Cardiac Marker in HIV Patients

The acute phase protein α2-macroglobulin induces rat ventricular cardiomyocyte hypertrophy via ERK1,2 and PI3-kinase/Akt pathways☆

Effects of Lead and Mercury on the Blood Proteome of Children

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