Basic research studies to understand aneurysm disease.
Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with life-threatening implications. Aneurysms typically have no signs or symptoms, and rupture of AAA has a high mortality rate. Multiple environmental and genetic risk factors are involved in aneurysm formation and progression making it a complicated disease to study. Little is understood about the mechanisms in disease initiation, thus there are currently no therapeutic approaches to prevent AAA, leaving patients with surgery as their only option. Ongoing research into the genetic components of AAA using a candidate gene approach has been overall unsuccessful. A more promising approach to study complex diseases involves genome-wide techniques such as DNA linkage analysis, genetic association studies and microarray expression profiling. Furthermore, studies involving inhibition of AAA progression, rather than formation, have a potentially promising outcome. Targeting biological pathways in AAA pathogenesis may benefit patients by slowing the growth and possibly preventing the rupture of AAA. Critical pathways involved in AAA pathogenesis include immunological processes, such as T-cell and natural killer cell pathways, oxidative stress, depletion of vascular smooth muscle cells through the process of apoptosis and the destruction of the extracellular matrix by matrix metalloproteinases.
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Amy M
AM
Boddy
Guy M
GM
Lenk
John H
JH
Lillvis
Jennifer
J
Nischan
Yoshiki
Y
Kyo
Helena
H
Kuivaniemi
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology
D016326:Extracellular Matrix Proteins; D020782:Matrix Metalloproteinases