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Am J Transl Res 2013;5(1):1-14
Review Article
Atherofibrosis - a unique and common process of the disease
patho-genesis of atherosclerosis and fibrosis - lessons for biomarker
devel-opment
Efstathios Vassiliadis, Natasha Barascuk, Morten A Karsdal
Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, Denmark; University of Southern Denmark, Odense,
Denmark
Received December 4, 2012; Accepted December 27, 2012; Epub January 21, 2013; Published January 30, 2013
Abstract: The hallmark of a variety of fibrotic diseases such as liver fibrosis, lung fibrosis, skin fibrosis and
atherosclerosis is extensive extracellular matrix remodeling (ECMr) of the disease affected tissue. Inflammation
often leads to tissue disruption and destruction, upon which locally released battery of proteases such as matrix
metalloproteinases and cysteine proteases degrade the surrounding matrix. The degradation products of ECM
proteins, the co-called neoepitopes, are released into the systemic circulation. By recent development of
Enzyme-Linked Immunosorbent Assays (ELISAs) detecting the pathological tissue turnover in atherosclerosis
and liver fibrosis, we have introduced a novel class of biomarkers into the field of fibrotic diseases, which have
been proved efficient in the early diagnosis. This work has resulted in identification of common mechanisms
involving specific cell types, proteins and proteases as well as pathways shared among the fibrotic diseases. In
this analysis we seek to answer following questions: a) Are there common disease mechanisms and cell types
involved in both atherosclerosis and fibrosis? b) Can the lessons learned in developing fibrosis biomarkers be
used for the development of atherosclerosis biomarkers? Our hypothesis is that by answering the above
questions, we may be able to improve general understanding of the early-stage disease initiation and
progression of fibrotic diseases, which in turn may aid in early diagnosis, prognosis and ultimately patient
management. (AJTR1212002).
Keywords: Atherosclerosis, fibrosis, extracellular matrix, collagens, proteoglycans, matrix metalloproteinases,
neoepitopes, biomarkers
Address correspondence to: Dr. Efstathios Vassiliadis, Nordic Bioscience A/S, Herlev Hovedgade 207, 2730
Herlev, Denmark. Phone: (45) 44547738; Fax: (45) 44525251; E-mail: eva@nordicbioscience.com
Review Article
Atherofibrosis - a unique and common process of the disease
patho-genesis of atherosclerosis and fibrosis - lessons for biomarker
devel-opment
Efstathios Vassiliadis, Natasha Barascuk, Morten A Karsdal
Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, Denmark; University of Southern Denmark, Odense,
Denmark
Received December 4, 2012; Accepted December 27, 2012; Epub January 21, 2013; Published January 30, 2013
Abstract: The hallmark of a variety of fibrotic diseases such as liver fibrosis, lung fibrosis, skin fibrosis and
atherosclerosis is extensive extracellular matrix remodeling (ECMr) of the disease affected tissue. Inflammation
often leads to tissue disruption and destruction, upon which locally released battery of proteases such as matrix
metalloproteinases and cysteine proteases degrade the surrounding matrix. The degradation products of ECM
proteins, the co-called neoepitopes, are released into the systemic circulation. By recent development of
Enzyme-Linked Immunosorbent Assays (ELISAs) detecting the pathological tissue turnover in atherosclerosis
and liver fibrosis, we have introduced a novel class of biomarkers into the field of fibrotic diseases, which have
been proved efficient in the early diagnosis. This work has resulted in identification of common mechanisms
involving specific cell types, proteins and proteases as well as pathways shared among the fibrotic diseases. In
this analysis we seek to answer following questions: a) Are there common disease mechanisms and cell types
involved in both atherosclerosis and fibrosis? b) Can the lessons learned in developing fibrosis biomarkers be
used for the development of atherosclerosis biomarkers? Our hypothesis is that by answering the above
questions, we may be able to improve general understanding of the early-stage disease initiation and
progression of fibrotic diseases, which in turn may aid in early diagnosis, prognosis and ultimately patient
management. (AJTR1212002).
Keywords: Atherosclerosis, fibrosis, extracellular matrix, collagens, proteoglycans, matrix metalloproteinases,
neoepitopes, biomarkers
Address correspondence to: Dr. Efstathios Vassiliadis, Nordic Bioscience A/S, Herlev Hovedgade 207, 2730
Herlev, Denmark. Phone: (45) 44547738; Fax: (45) 44525251; E-mail: eva@nordicbioscience.com
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