Role of hyperhomocysteinemia in aortic disease.
A growing body of evidence has shown a strong association between elevated plasma homocysteine (Hcy) levels with vascular disease and thrombotic complications. Data available in literature also suggest a role of hyperhomocysteinemia in abdominal and thoracic aortic diseases. In particular, Hcy was investigated in patients with Marfan syndrome and it was demonstrated that Hcy levels were associated with the risk of severe cardiovascular manifestations or dissection. Hcy was significantly higher also in patients with abdominal aortic aneurysms and was associated with the size of aneurysms. It remains to be elucidated if this association is causal or simply an effect of the disease. A number of mechanisms may be evoked to explain these findings. Studies in animal models demonstrated that hyperhomocysteinemia could induce marked remodelling of the extracellular matrix of the arterial wall by inducing elastolysis through the activation of metalloproteinases. In addition, Hcy may directly affect fibrillin-1 or collagen by interfering with intra- and/or inter-molecular disulfide bonds through disulfide exchange, or binding to free sulphydryl groups. Further studies are needed to confirm the role of Hcy in aortic disease and the usefulness of including Hcy determination in the clinical evaluation of these patients.
Giusti
B
B
Department of Medical and Surgical Critical Area, University of Florence, viale Morgagni 85, 50134 Florence, Italy. b.giusti@dac.unifi.it
Marcucci
R
R
Lapini
I
I
Sestini
I
I
Lenti
M
M
Yacoub
M
M
Pepe
G
G
D000368:Aged; D000818:Animals; D001011:Aorta / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000150:complications; D001018:Aortic Diseases / Q000150:complications* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005838:Genotype; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications*; D008297:Male; D008382:Marfan Syndrome / Q000150:complications; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D012306:Risk; D013927:Thrombosis / Q000150:complications; D014652:Vascular Diseases / Q000150:complications; D054392:Adipokines
D003094:Collagen; D000071838:Fibrillin-1; D000071837:Fibrillins; D006710:Homocysteine; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines