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(Circulation Research. 2008;102:869.)
© 2008 American Heart Association, Inc.

Editorials

Hyperhomocysteinemia and Occlusive Vascular Disease

An Emergent Role for Fibroblast Growth Factor 2

Miguel Ángel Medina

From Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain.

Correspondence to Miguel Ángel Medina, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, E-29071 Málaga, and CIBER de Enferemedades Raras (CIBERER), Málaga, Spain. E-mail medina@uma.es

See related article, pages 933–941

Key Words: homocysteine • FGF2 • endothelial cell • G protein • DNA methylation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Occlusive vascular disease is the leading cause of mortality and disability in the Western world. Based in accumulated previous evidence, in 1991 Clarke et al identified hyperhomocysteinemia as a new independent risk factor for vascular disease.¹ Since then, hyperhomocysteinemia has been associated with an increased risk of cardiovascular disease, including atherosclerosis, thrombosis, stroke, and peripheral arterial occlusive disease.^2–5 However, there is no clear consensus as to the potential mechanisms, whereby excess homocysteine could contribute to vascular disease,^5,6 although endothelial cell damage and/or injury should be expected. In the absence of a clear mechanism linking homocysteine to cardiovascular disease, controversy remains concerning the actual role of hyperhomocysteinemia as an independent or a conditional risk factor or simply a marker of cardiovascular disease.^1,6–8 In the present issue of Circulation Research, Chang et al⁹ show that a specific homocysteine-induced downregulation of fibroblast growth factor (FGF)2 disrupts endothelial integrity by both decreasing endothelial cell proliferation and inducing endothelial cell apoptosis. Recently, it has been claimed that new studies providing insight into the regulatory effects of elevated homocysteine levels are crucial for the development of new diagnostic and therapeutic methods.⁵ In this sense, the report by Chang et al⁹ adds relevant and valuable information, unveiling FGF2 gene expression as a specific molecular target of homocysteine at pathophysiological levels.

At the molecular level, several potential mechanisms have been proposed previously, including induction of endoplasmic reticulum stress and unfolded protein response (UPR), protein N-homocysteinylation, and epigenetic effects concerning methylation status.^4,5,10–12 Until now, the connection of . . . [Full Text of this Article]