A STUDY ON THE INTRIGUING PATHOGENIC RELATIONSHIP repository- Diabetes mellitus. The major lipids of

download A STUDY ON THE INTRIGUING PATHOGENIC RELATIONSHIP repository- Diabetes mellitus. The major lipids of

of 164

  • date post

    11-Jan-2020
  • Category

    Documents

  • view

    1
  • download

    0

Embed Size (px)

Transcript of A STUDY ON THE INTRIGUING PATHOGENIC RELATIONSHIP repository- Diabetes mellitus. The major lipids of

  • A STUDY ON THE INTRIGUING PATHOGENIC RELATIONSHIP BETWEEN

    LIPOPROTEIN (a) AND TRANSFORMING GROWTH FACTOR-β IN

    ATHEROSCLEROTIC PERIPHERAL VASCULAR DISEASE    

    Dissertation submitted to 

    THE TAMILNADU Dr. MGR MEDICAL UNIVERSITY  in partial fulfilment for  the award of degree of 

    DOCTOR OF MEDICINE IN BIOCHEMISTRY 

    BRANCH XIII   

             

    INSTITUTE OF BIOCHEMISTRY  MADRAS MEDICAL COLLEGE 

    CHENNAI – 600 003     

    APRIL 2012 

  • THE TAMILNADU Dr.MGR MEDICAL UNIVERSITY  BONAFIDE CERTIFICATE 

    This is to certify that this dissertation work entitled A STUDY ON THE

    INTRIGUING PATHOGENIC RFELATIONSHIP BETWEEN LIPOPROTEIN (a)

    AND TRANSFORMING GROWTH FACTOR-β IN ATHEROSCLEROTIC

    PERIPHERAL VASCULAR DISEASE is the original bonafide work done by

    Dr.VEENA JULIETTE.A, Post Graduate Student, Institute of Biochemistry, Madras

    Medical College, Chennai under our direct supervision and guidance.

     

     

     

     

    Dr. Pragna B. Dolia, M.D., The Dean

    Director and Professor, Madras Medical College and

    Institute of Biochemistry, Rajiv Gandhi Govt. Gen Hospital

    Madras Medical College, Chennai- 600 003.

    Chennai- 600 003.

    GUIDE

     

     

     

  • SPECIAL ACKNOWLEDGEMENT

    The author gratefully acknowledges and sincerely thanks Professor Dr. V.

    Kanagasabai M.D, Dean, Madras Medical College and Rajiv Gandhi Govt.

    General Hopsital, and Professor Dr.V.Palani, M.S., Medical Superintendent, Rajiv

    Gandhi Government General Hospital, Chennai, for granting her permission to

    utilize the facilities of this Institution for the study.

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

  • ACKNOWLEDGEMENT 

    With due respect the author deems it a privilege to thank Professor Dr.Pragna B.

    Dolia, M.D., Director, Institute of Biochemistry, Madras Medical College, Chennai, from

    the bottom of her heart for having stood by her throughout the preparation of this study

    and bestowing her able guidance, constant encouragement, support and valuable time but

    for which this dissertation could not have been made possible.

    The author owes her sincere thanks to Dr.K.Ramadevi, M.D., Professor, Institute

    of Biochemistry, Madras Medical College, for having helped her in the indecisive task of

    selecting an appropriate topic and extending her able guidance and valuable suggestions

    throughout the course of this study.

    The author expresses her sincere thanks to Dr.M.Shyamraj, M.D., Professor,

    Institute of Biochemistry, for his motivation and support for this study.

    The author expresses her profound gratitude to Dr. R.Chitraa, M.D., Professor,

    Institute of Biochemistry for her encouragement and support.

    The author conveys her gratitude to Dr. Amudhavalli, M.D., Associate Professor,

    Institute of Biochemistry, for her ample support and encouragement.

    The author is extremely thankful to Dr.T.Vidyasagaran, M.S, M.Ch., Professor and

    Head of the Department, Department of Vascular Surgery, Rajiv Gandhi Government

    General Hospital, Chennai, for granting permission to obtain blood samples from the

    patients.

  • The author conveys immense gratitude to Dr. Sivachidambaram, M.D, D.M., Head

    of the Department of Mater Health Check-Up, Rajiv Gandhi Government General

    Hospital, Chennai, for having granted permission to obtain blood samples from healthy

    controls and extending constant support for the completion of this study.

    Profuse thanks are due to Dr.V.K.Ramadesikan, M.D., Associate Professor,

    Institute of Biochemistry, for his never ending support and constructive thinking that

    helped the author carry out this study with confidence.

    The author extends her sincere thanks to Dr.S.Sumathy, M.D., Assistant Professor,

    Institute of Biochemistry, for her guidance and support for carrying out this study.

    The author owes her humble and profound gratitude to Dr.C.Shanmugapriya,

    M.D., Assistant Professor, Institute of Biochemistry, for extending her overwhelming

    brilliance and excellent ideas that helped the author immensely to bring forward this

    piece of quality assignment.

    A deep sense of gratitude to Dr.V.Ananthan, M.D., Assistant Professor, Institute of

    Biochemistry, for having helped the author in this endeavor of hers, every step of it

    including the practical analysis and statistics, without him this study would not have

    gained its full dimensions.

    The author expresses her warm respects and sincere thanks to Dr. Poonguzhali

    Gopinath, M.D., and Dr.V.G.Karapaghavalli, M.D., Assistant Professors, Institute of

    Biochemistry, Madras Medical college for their guidance and constant encouragement.

  • The author expresses her special thanks to Dr.Chithra, M.S.,(M.Ch) ., Post

    Graduate, Department of Vascular Surgery, for helping her selecting appropriate cases

    for this study.

    The author gratefully acknowledges the help rendered by her colleagues and

    juniors for their immense help, constant encouragement and unconditional support

    throughout the study.

    A special thanks to all the technical staff of the Central Biochemistry Lab, Rajiv

    Gandhi Government General Hospital, Chennai.

    The author is indebted to the patients and the persons from whom blood samples

    were collected for conducting the study.

    Finally, the author dedicates her entire work and her heartfelt gratitude at the

    lotus feet of her parents Mr. C.Amaladoss, M.A. M.Phil., and Mrs. M.Susaimary, M.Sc,

    M.Ed, M.Phil., for they are the driving force behind her, not only for this study but for

    every step she takes ahead in life.

    The author renders her Thankful prayers to the God Almighty for steadily

    guiding her along every minute of the day, through the Universe, and from Inside.

     

     

     

     

     

     

  •  

    ABBREVIATION 

    PVD  ‐       Peripheral Vascular Disease 

    ABPI  ‐  Ankle Brachial Pressure Index 

    VLDL   –  Very Low Density Lipoprotein 

    LDL  –  Low Density Lipoprotein 

    HDL   –  High Density Lipoprotein 

    Lp(a)  ‐  Lipoprotein (a) 

    TGF‐β  ‐  Transforming Growth Factor‐β 

    TNF‐α   –  Tumour Necrosis Factor‐α 

    DM  –  Diabetes Mellitus 

    SMK  –  Smoking 

    ALC  –  Alcoholism 

    WT  –  Weight 

    HT  –  Height 

    BMI  –  Body Mass Index 

    CHOL  –  Cholesterol 

    TGL  –  Triglyceride 

    ER  –  Endoplasmic reticulum 

    IL  ‐  Interleukin 

    TLR  ‐  Toll Like Receptor 

    NF‐κB  ‐  Nuclear Factor κB 

    IFN  ‐  Interferon 

     

  •  

     

     

    INDEX 

     

     

    Page No. 

    1. INTRODUCTION  1 

    2. REVIEW OF LITERATURE  3 

    3. AIM OF THE STUDY  47 

    4. MATERIALS AND METHODS  49 

    5. STATISTICAL ANALYSIS  65 

    6. RESULTS  66 

    7. DISCUSSION  69 

    8. CONCLUSION  73 

              9.    FUTURE PROSPECTS OF THE STUDY                                                                       74 

                                        

     

     

     

  • INTRODUCTION  

     

     

     

     

     

     

     

     

     

     

  • INTRODUCTION

    Peripheral Vascular Disease (PVD), or Peripheral Arterial disease, is one of the

    major causes of morbidity and mortality in the Indian population, the prevalence

    increasing in elderly and diabetic people. Chronic lower extremity ischemia is the most

    common cause of loss of walking ability attended by a vascular surgeon and is associated

    with a constellation of disorders affecting the entire system1. Atherosclerotic PVD is a

    prototype of chronic systemic atherosclerosis and is characterized by arterial stenoses and

    occlusions in the peripheral arterial bed of lower limbs. The various risk factors include

    Age, DM, Smoking, hypertension, hyperlipidemia, hyperhomocysteinemia etc.

    Atherosclerosis is a chronic inflammatory disease. Cardiovascular atherogenicity

    is the major cause of mortality around the world, though it can effect all the medium and

    large sized vessels in the body. Dyslipidemia is a major risk factor for the development

    and progression of atherosclerosis, along with the life style and co morb