Profile

Research

Publications

Team

Alumni

C C Kartha, MD, FRCP

Honorary Distinguished Professor

+91-471-2529448

cckartha@rgcb.res.in

Dr-C-C-Kartha
Dr-C-C-Kartha

C C Kartha, MD, FRCP

Honorary Distinguished Professor

+91-471-2529448

cckartha@rgcb.res.in

  • Profile

    • MD (Pathology) – 1979 (All India Institute of Medical Sciences, New Delhi)
    • MBBS – 1974 (Trivandrum Medical College, Kerala University)
    • From 14 January 2009: Professor of Eminence, Rajiv Gandhi Center for Biotechnology, Trivandrum
    • October 2006 – 13 January 2009: Senior Grade Professor & Head, Division of Cellular & Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum
    • Dec 2000 to Dec 2003: Dean, Academic Affairs, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum
    • 1993-2006: Professor & Head, Division of Cellular & Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum
    • 1988-93: Additional Professor in Pathology, Sree Chitra Tirunal Institute for Medical Sciences &Technology, Trivandrum
    • 1986-88: Associate Professor in Pathology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum
    • 1982-85: Assistant Professor in Pathology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum
    • 1979-82: Lecturer in Pathology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum
    • Fellow, Royal College of Physicians (London)
    • Fellow, International Academy of Cardiovascular Sciences (Canada)
    • Fellow, National Academy of Medical Sciences, India
    • Fellow, Indian Academy of Sciences
    • Fellow, National Academy of Sciences (India)
    • Fellow, Pulmonary Vascular Research Institute (United Kingdom)
    • Fellow, Indian College of Pathology
    • Oration Award, IAPM Orissa chapter
    • Invited Speaker, World Congress of International Society for Heart Research, Winnipeg, 2001
    • Invited Speaker and Symposium Chairman, World Congress of International Society for Heart Research, Brisbane 2004
    • Invited Speaker, Global conference on Heart Health and Diseases, Winnipeg 2006
    • Invited Speaker, New Biology Symposium, Indian Science Congress 2008
    • Invited Speaker and Symposium Chair, World Congress of International Academy of Cardiovascular Sciences, Copenhagen 2009 and Vadodara, India 2011
    • Invited Speaker, Winnipeg International Heart Conference, Winnipeg 2011
    • Prof. Manjeet Singh Oration Award, International Society for Heart Research- Indian Section 2014
    • Fellow, Royal College of Physicians (London)
    • Distinguished Leadership Award in Cardiovascular Science, Medicine and Surgery, International Academy of Cardiovascular Sciences, Canada 2015
    • Member, Editorial Board, Molecular and Cellular Biochemistry, Springer 2010
    • Member, Editorial Advisory Board, Pulmonary Circulation, Medknow Publishers 2010
    • Member, Editorial Advisory Board, The Open Nitric Oxide Journal, Bentham Publishers 2008
    • Co-Chairman, Expert Group on Cardiac, Renal and Metabolic Diseases, Chronic Disease Biology Task Force, DBT, India
    • Chairman, Research Council for Science and Engineering, Kerala State Council for Science, Technology and Environment 2013.
    • Chairman, Young Scientist Scheme, Kerala State Council for Science, Technology and Environment 2013.
    • Chairman, Human Ethics Committee, Central University, Kasargode.
    • Member, Advisory Committee, Department of Bioengineering, Indian Institute of Technology, Hyderabad.
    • Member, Project Review Committee for Cardiovascular Diseases, Indian Council of Medical Research 2008
    • Indian Co-Chair of ICMR Review Committee for Indo Canadian Research projects on Childhood Obesity
    • Member (Chancellor's nominee), Academic Council, Kerala University of Health Sciences 2011-2015
    • Member, Scientific Advisory Committee, National Institute of Nutrition (Indian Council of Medical Research) Hyderabad 2011
    • Member, State Biomedical Research Board, Kerala 2010-2014
    • Chairman, State Level Review Board for Clinical Research, Government of Kerala
    • Member, Board of studies in Biotechnology, Cochin University of Science & Technology
    • Chairman, Institutional Human Ethics Committee, PMS College of Dental Sciences & Research 2010.
    • Member, Human Ethics Committee, Regional Cancer Center, Thiruvananthapuram 2010- 2014
    • Area Panel Reviewer, Biotechnology Industry Partnership Program, Department of Biotechnology, India 2010
    • Member, Biotechnology Commission, Government of Kerala 2011
    • Vice President, Indian Section of International Society for Heart Research, 2013
    • Vice President, Indian Section of International academy of Cardiovascular Sciences, 2014
    • Trained in pulmonary vascular pathology (University of Liverpool, UK) Professional Record
    • Trained in cardiac electron microscopy at (National Heart, Lung & Blood Institute, Bethesda, USA)
  • Research

    Research Intrests

    Medical Biotechnology, Molecular Cardiology, Cardiovascular disease biology, Endothelial pathobiology, Cardiac stem cells and Cell based therapies for cardiovascular diseases.

    Research Themes

    • Macrovascular disease and chronic Inflammation in Type 2 Diabetes Mellitus

    A major program of our group is the research on identification of cellular and molecular markers for the early detection of vascular disease in patients with type-2 diabetes. The aim is to discover screening markers and possibly develop diagnostic tools as well as strategies to reduce the risk. The major themes envisioned to achieve this goal are:

    • Monocyte proteins as markers of detecting vascular complications in type 2 diabetes

    Immune-inflammatory response, the initial reaction to tissue injury, characterized by monocyte-macrophage activation, plays a key role in the pathogenesis of vascular disease in type 2 diabetes. Circulating monocytes can de?ne innate immune-mediated processes by secreting immune regulatory bioactive factors which include secretory proteins, interferons, interleukins, growth factors, and chemokines.We speculate that alterations in monocyte protein profiles can be used as early predictors of vascular diseases.

    • Gut microbiota in type 2 diabetes mellitus

    Another area of research in our laboratory is exploring our gut microbial communities to understand its involvement in the development of type 2 diabetes. Imbalance in gut microbiota composition may produce different inflammatory and epigenetic changes which may play a role in the pathogenesis of type 2 diabetes mellitus. We focus on epigenetic mechanisms by which gut microbiota modulates gene expression in insulin synthesis pathways in pancreatic islets

    • Vascular biology and remodeling of cardiac endothelium in heart failure.

    Research in the vascular biology group focuses on deciphering the role of cardiac endothelial cells in myocardial remodeling in progressive heart failure. The group focuses on the mechanisms of endothelial dysfunction and various cellular and molecular changes that occur in the cardiac endothelial cells during evolution of cardiac hypertrophy in pressure overload and during decompensation stages resulting in cardiac failure. The vascular biology theme is also linked to studies on the molecular basis of remodeling of pulmonary vascular endothelium in left ventricular heart failure.

    Our major strategies for attaining this goal are:

    • Creation of pressure overload rat animal model with left- ventricular heart failure and associated pulmonary hypertension.
    • Molecular analysis of cardiac and vascular tissue in cardiac hypertrophy and pulmonary hypertension.
    • Defining the role and contribution of the vasculature during the remodeling process.
    • Exploring novel pharmacological therapies to reverse adverse pressure-induced hypertrophic myocardial and vascular remodeling.
    • Evaluation ofayurvedic medicines such asAmalakirasayanato reverse pathological cardiac remodeling associated with cardiac failure and aging.
    • Endogenous stem cell populations capable of differentiating into cardiomyocytes in the adult mammalian heart as a therapeutic target for cardiac repair
    • Identifying dysregulated signalling molecules and transcription factors leading to pathogenesis of congenital heart disease and subsequent heart failure

    Grants Present

    1. Funded by DST, India: Can Amalaki Rasayana attenuate cardiac dysfunction associated with cardiac failure and aging?

    Recent Past

    1. Funded by DBT, India: Remodeling of cardiac endothelium in progressive heart failure
    2. Funded by ICMR, India: A proteomic analysis of circulating cells for the discovery of biomarkers of increased risk of atherosclerosis in patients with type 2 diabetes mellitus
    3. Funded by DBT, India: Adult human resident cardiac stem cells and endothelial progenitor cells: detection of optimum conditions for their therapeutic use
    4. Funded by Kerala State Council for Science, Technology & Environment: Modulation of high glucose induced monocyte chemoattractant protein-1 gene expression in aortic endothelial cells

    Past

    1. Funded by DST, India: Molecular basis of endomyocardial fibrosis
    2. Funded by BRNS, DAE: Vitamin D and its relationship to coronary artery disease in a tropical population
    3. Funded by Indian Council of Medical Research: Experimental eosinophilia in Wistar rats; Developing an animal model for endomyocardial fibrosis
    4. Funded by Lady Tata Memorial Trust: Immunological studies in endomyocardial fibrosis
  • Publications

    Books: AU: 1; Edited: 4; Chapters in books: 14; Reviews: 14; Focussed Editions of Journals edited: 2; Original research publications: 64; Case reports: 10; Other contributions: 30

    Recent Publications (2011-2014)

    1. Ramachandran S, Venugopal A, Ramankutty V, Vinitha A, Divya G, V Chitrasree, AjitMullassari, N S PratapChandran, K R Santosh, M Radhakrishna Pillai, C CKartha. Plasma Level of Cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease. Cardiovasc Diabetol 2014;13:38.
    2. Ann Mary Johnson and C. C. Kartha. Proliferation of murine c-kit pos cardiac stem cells stimulated with IGF-1 is associated with Akt-1 mediated phosphorylation and nuclear export of FoxO3a and its effect on downstream cell cycle regulators. Growth Factors 2014 (doi: 10.3109/08977194.2014.889694).
    3. Ajithkumar GS*, Binil Raj*, Santhosh Kumar S, Sanjay G & Kartha CC. Ascending aortic constriction in rats for creation of pressure overload cardiac hypertrophy model. Journall of Visualized Experiments 2014;e50983:1-7.
    4. Sumi S, Athira G, Radhakrishnan N, Kalpana SR, Divya Nair H, Jissa VT, Kartha CC. Forkhead box C2 promotervariant c.-512C>T is associated with increased susceptibility to chronic venous diseases. PLOS One 2014;9:e90682.
    5. Kshemada K, Kartha CC and Mehta JL. Editorial: Forensic Sciences and growth of Cardiology. J Forensic Res 2013; 5: 1000e115.
    6. Padmaja Parameswaran Nampi, Cheranellore Chandrasekharan Kartha, Gin Josec, Anil Kumar PR, Thapasimuthu Anilkumara, Harikrishna Varma. Sol–gel nanoporous silica as substrate for immobilization of conjugatedbiomolecules for application as fluorescence resonance energy transfer (FRET) based biosensor. Sensors and Actuators B 2013; 185: 252– 257.
    7. Prabha Nini Gupta, Kumaralingam G Balakrishnan and Kartha CC. Decreased protein C levels in endomyocardial fibrosis: The possible significance. Blood Disorders Transf 2013;4:6. http://dx.doi.org/10.4172/2155-9864.1000170
    8. Ramachandran S, Venugopal A, K Sathisha , G Reshmi, Charles S, G Divya, Chandran NS, Mullassari A, Pillai MR, Kartha CC. Proteomic profiling of high glucose primed monocytes identifies cyclophilin A as a potential secretory marker of inflammation in type 2 diabetes. Proteomics 2012;12:2808-21.
    9. Ramachandran S, Kartha CC. Cyclophilin-A: a potential screening marker for vascular disease in type-2 diabetes. Can J Physiol Pharmacol 2012;90:1005-15.
    10. Binil Raj, Harikrishnan Sivadasan Pillai and Chandrasekharan Cheranellore Kartha. Molecular basis of pulmonary hypertension in left heart failure. In N.S. Dhalla et al. (eds.), Molecular Defects in Cardiovascular Disease. Springer Science 2011; 259-71.
    11. Gopinathan nair Santhambika Ajithkumar, Surya Ramachandran, Cheranellore Chandrasekharan Kartha. Drug induced endothelial dysfunction: functional role of oxidative stress. The IIOAB Journal 2011;2:62–70.
    12. Savneet Kaur, VS Harikrishnan, Sachin J Shenoy, NS Radhakrishnan, Akira Uruno, Akira Sugawara and Chandrasekharan C Kartha. Transfection of endothelial nitric oxide synthase gene improves angiogenic efficacy of endothelial progenitor cells in rabbits with hindlimb ischemia. J Clinic Exp Cardiol 2011;2:140. doi:10.4172/2155-9880.1000140.
    13. Sathish Kumar Maney, Ann Mary Johnson, A. Sampath Kumar, Vineet Nair, TR. Santhosh Kumar and CC. Kartha. Effect of apoptosis-inducing anti tumor agents on endocardial endothelial cells. Cardiovasc Toxicol 2011;11:253–262.
    14. Jeemon P, Prabjakaran D, Ramakrishnan L, Gupta R, Ahmed F, Thankappan KR, Kartha CC, Chaturvedi V and Reddy KS. Association of high sensitive C- reactive protein (hsCRP) with established cardiovascular risk factors in Indian population. Nutrition and Metabolism 2011; 8:19-26.
  • Team


    Dr. Ajith Kumar G S, MVSc, CSIR-SRF

    Antioxidative and antiapoptotic effect of endothelial mediators in cardiac hypertrophy and heart failure

    Endocardial endothelial (EEC) cells and the micro vascular endothelial cells (MVEC) are the two different types of endothelial cells influencing heart’s function. Both are involved in modulation of myocardial performance by autocrine and paracrine mediators. Endocardial endothelial cells regulate underlying myocardial cells and are structurally and functionally dissimilar from vascular endothelial cells. Endocardial endothelial cells are continuously exposed to the flowing blood in the heart and thus serve as a sensor of signals such as shear stress, vasoactive substances, inflammatory molecules and oxidizing and antioxidizing agents.Endocardial endothelial cell dysfunction is seen similarly as micro vascular endothelial cell dysfunction in pathological conditions of heart. The structural and functional status of the EECs appreciably influences the outcome in various pathological conditions. I propose to analyze the functional significance of candidate mediator molecules of EEC origin in myocardial performance under oxidative stress conditions as well as in cardiac hypertrophy and heart failure.

    ajith kumar GS
    ajith kumar GS

    Dr. Ajith Kumar G S, MVSc, CSIR-SRF

    Antioxidative and antiapoptotic effect of endothelial mediators in cardiac hypertrophy and heart failure

    Endocardial endothelial (EEC) cells and the micro vascular endothelial cells (MVEC) are the two different types of endothelial cells influencing heart’s function. Both are involved in modulation of myocardial performance by autocrine and paracrine mediators. Endocardial endothelial cells regulate underlying myocardial cells and are structurally and functionally dissimilar from vascular endothelial cells. Endocardial endothelial cells are continuously exposed to the flowing blood in the heart and thus serve as a sensor of signals such as shear stress, vasoactive substances, inflammatory molecules and oxidizing and antioxidizing agents.Endocardial endothelial cell dysfunction is seen similarly as micro vascular endothelial cell dysfunction in pathological conditions of heart. The structural and functional status of the EECs appreciably influences the outcome in various pathological conditions. I propose to analyze the functional significance of candidate mediator molecules of EEC origin in myocardial performance under oxidative stress conditions as well as in cardiac hypertrophy and heart failure.

    Shammy S, MSc, UGC-SRF

    Molecular mechanisms in the pathogenesis of Tetralogy of Fallot

    Congenital heart disease refers to abnormalities in the heart’s structure or function that arise before birth. Congenital heart diseases are the leading non- infectious cause of death in children in their first year of life.Tetralogy of Fallot (TOF) is a congenital conotruncal anomaly with an incidence of 3 per 10,000 live births. Narrowing of the sub pulmonic infundibulum of right ventricle is characteristic of tetralogy of Fallot. Transcription factors, signaling molecules, and structural proteins involved in embryonic development of right ventricular outflow tract (RVOT) could be key candidates in the pathogenesis of infundibular stenosis from increased muscle mass in the region. I am investigating through mutational analysis, whether there is any link between cardiac lesions in tetralogy of Fallot and the genes involved in the development of the right ventricular outflow tract. To elucidate the causal factors for regional muscle growth, the gene expression pattern of cardiac transcription factors and proteomic profile of RVOT myocardium of patients with TOF are also being analyzed.

    Shammy S
    Shammy S

    Shammy S, MSc, UGC-SRF

    Molecular mechanisms in the pathogenesis of Tetralogy of Fallot

    Congenital heart disease refers to abnormalities in the heart’s structure or function that arise before birth. Congenital heart diseases are the leading non- infectious cause of death in children in their first year of life.Tetralogy of Fallot (TOF) is a congenital conotruncal anomaly with an incidence of 3 per 10,000 live births. Narrowing of the sub pulmonic infundibulum of right ventricle is characteristic of tetralogy of Fallot. Transcription factors, signaling molecules, and structural proteins involved in embryonic development of right ventricular outflow tract (RVOT) could be key candidates in the pathogenesis of infundibular stenosis from increased muscle mass in the region. I am investigating through mutational analysis, whether there is any link between cardiac lesions in tetralogy of Fallot and the genes involved in the development of the right ventricular outflow tract. To elucidate the causal factors for regional muscle growth, the gene expression pattern of cardiac transcription factors and proteomic profile of RVOT myocardium of patients with TOF are also being analyzed.

    Ann Mary Johnson, MSc, CSIR-SRF

    Mechanisms of Cell Cycle Regulation in Cardiac Stem cells

    Identification of cardiac stem cells changed the paradigm of heart as a post mitotic organ. c-kitposcardiac stem cells possess self renewal capability and multipotency. c-kitposcardiac stem cells are undifferentiated cells with tightly orchestrated expressions of early cardiac specific genes. After birth, these stem cells remain quiescent until they are stimulated to proliferate and differentiate into cardiomyocytes. In postnatal murine heart cardiomyocyte turn over occurs at a rate of ~1- 4% / year. Mechanisms that initiate and cease proliferation of cardiac stem cells are largely unknown. FoxO family transcription factors have been reported to regulate stem cell homeostasis during adulthood. However, its function in cardiac stem cells remains obscure. Our research aims on elucidating the molecular basis of cell cycle program involving Forkhead family ‘O’ class transcription factors in cardiac stem cells. Unraveling the mechanisms of cardiac stem cell homeostasis during development may contribute to stem cell research towards an improved understanding of intrinsic regenerative mechanisms in heart.

    Ann Mary Johnson
    Ann Mary Johnson

    Ann Mary Johnson, MSc, CSIR-SRF

    Mechanisms of Cell Cycle Regulation in Cardiac Stem cells

    Identification of cardiac stem cells changed the paradigm of heart as a post mitotic organ. c-kitposcardiac stem cells possess self renewal capability and multipotency. c-kitposcardiac stem cells are undifferentiated cells with tightly orchestrated expressions of early cardiac specific genes. After birth, these stem cells remain quiescent until they are stimulated to proliferate and differentiate into cardiomyocytes. In postnatal murine heart cardiomyocyte turn over occurs at a rate of ~1- 4% / year. Mechanisms that initiate and cease proliferation of cardiac stem cells are largely unknown. FoxO family transcription factors have been reported to regulate stem cell homeostasis during adulthood. However, its function in cardiac stem cells remains obscure. Our research aims on elucidating the molecular basis of cell cycle program involving Forkhead family ‘O’ class transcription factors in cardiac stem cells. Unraveling the mechanisms of cardiac stem cell homeostasis during development may contribute to stem cell research towards an improved understanding of intrinsic regenerative mechanisms in heart.

    Binil Raj S S, M Pharm, ICMR-SRF

    Molecular basis of remodelling of pulmonary vascular endothelium in left heart failure

    In patients with left heart failure, elevation in left ventricular filling pressure results in reactive increase in pulmonary vascular resistance leading to pulmonary hypertension (PH). This secondary PH may reflect remodeling of pulmonary vascular wall resulting in vascular stiffness and reduced vasodilator responsiveness. About two thirds of patients with left ventricular (LV) failure have associated PH. The mortality in patients with LV failure with PH is two fold higher compared to mortality in patients with LV failure without PH. Considerable evidence indicates that impairment of endothelial function is a major cause of pulmonary vascular remodeling in heart failure. I propose to study the nature of endothelial dysfunction in PH in LV failure and the molecular mechanism of microvascular remodeling in LV failure associated PH. Better understanding of molecular mechanisms may help in identifying strategies for reversal of pulmonary vasculature remodelling in progressive LV failure.

    Binil Raj SS
    Binil Raj SS

    Binil Raj S S, M Pharm, ICMR-SRF

    Molecular basis of remodelling of pulmonary vascular endothelium in left heart failure

    In patients with left heart failure, elevation in left ventricular filling pressure results in reactive increase in pulmonary vascular resistance leading to pulmonary hypertension (PH). This secondary PH may reflect remodeling of pulmonary vascular wall resulting in vascular stiffness and reduced vasodilator responsiveness. About two thirds of patients with left ventricular (LV) failure have associated PH. The mortality in patients with LV failure with PH is two fold higher compared to mortality in patients with LV failure without PH. Considerable evidence indicates that impairment of endothelial function is a major cause of pulmonary vascular remodeling in heart failure. I propose to study the nature of endothelial dysfunction in PH in LV failure and the molecular mechanism of microvascular remodeling in LV failure associated PH. Better understanding of molecular mechanisms may help in identifying strategies for reversal of pulmonary vasculature remodelling in progressive LV failure.

    Vinitha A, MSc, DBT Project SRF

    Remodeling of cardiac endothelium in progressive heart failure

    During the progression of heart failure ‘remodeling’ of the heart occurs at genomic, cellular and tissue levels and these ‘remodeling’ activities are adaptive mechanisms to normalise the pump function. But continuous remodeling leads to ventricular dilatation, hypertrophy and further contractile dysfunction. Cardiac endothelial cells produce molecular mediators that influence myocyte contractile function in normal and pathological conditions. So when we consider myocardial remodeling in progressive cardiac hypertrophy and heart failure, cardiac endothelial cell- myocyte cross-talk also needs to be addressed. In pressure overload heart, the damage to cardiac endothelial cells could lead to failure of their regulatory and modulator functions. These can have serious consequences in cardiac performance.In this context my studies are aimed at deciphering the role of cardiac endothelial cells in myocardial remodeling in pressure overload left ventricular hypertrophy and progressive heart failure.

    Vinitha A
    Vinitha A

    Vinitha A, MSc, DBT Project SRF

    Remodeling of cardiac endothelium in progressive heart failure

    During the progression of heart failure ‘remodeling’ of the heart occurs at genomic, cellular and tissue levels and these ‘remodeling’ activities are adaptive mechanisms to normalise the pump function. But continuous remodeling leads to ventricular dilatation, hypertrophy and further contractile dysfunction. Cardiac endothelial cells produce molecular mediators that influence myocyte contractile function in normal and pathological conditions. So when we consider myocardial remodeling in progressive cardiac hypertrophy and heart failure, cardiac endothelial cell- myocyte cross-talk also needs to be addressed. In pressure overload heart, the damage to cardiac endothelial cells could lead to failure of their regulatory and modulator functions. These can have serious consequences in cardiac performance.In this context my studies are aimed at deciphering the role of cardiac endothelial cells in myocardial remodeling in pressure overload left ventricular hypertrophy and progressive heart failure.

    Sreehari VG, DST project-Animal Handler

    I assist in animal experimental procedures such as anaesthetizing the animal, echocardiography, aortic banding. My work also involves rearing the animals, monitoring animal cage conditions and handling the experimental animals.

    Sreehari
    Sreehari

    Sreehari VG, DST project-Animal Handler

    I assist in animal experimental procedures such as anaesthetizing the animal, echocardiography, aortic banding. My work also involves rearing the animals, monitoring animal cage conditions and handling the experimental animals.

    Ciji Varghese, Manager (Technical Services)

    I am involved in preparation and processing of indent forms for purchase of consumables required in the laboratory as well as periodic monitoring of stock books and equipments. I also provide technical support for laboratory experiments.

    Ciji Varghese
    Ciji Varghese

    Ciji Varghese, Manager (Technical Services)

    I am involved in preparation and processing of indent forms for purchase of consumables required in the laboratory as well as periodic monitoring of stock books and equipments. I also provide technical support for laboratory experiments.

  • Alumni