A STUDY ON THE INTRIGUING PATHOGENIC RELATIONSHIP repository- Diabetes mellitus. The major lipids of
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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
INSTITUTE OF BIOCHEMISTRY MADRAS MEDICAL COLLEGE
CHENNAI – 600 003
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.
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.
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
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.
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
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
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