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(Circulation. 2004;110:2260-2265.)
© 2004 American Heart Association, Inc.

Basic Science for Clinicians

Insulin-Like Growth Factor-1 as a Vascular Protective Factor

Elena Conti, MD, PhD; Cinzia Carrozza, MD; Ettore Capoluongo, BSc; Massimo Volpe, MD; Filippo Crea, MD, FESC; Cecilia Zuppi, MD; Felicita Andreotti, MD, PhD, FESC

From the Department of Cardiovascular Diseases (E. Conti., F.C., F.A.) and the Department of Biochemistry and Clinical Biochemistry (C.C., E. Capoluongo, C.Z.), Catholic University; and the Division of Cardiology, 2nd Faculty of Medicine, University of Rome "La Sapienza" (M.V.), Rome, Italy.

Correspondence to Elena Conti, MD, PhD, Institute of Cardiology, Catholic University Medical School, Via Todi 60, 00181 Rome, Italy. E-mail e_conti02@hotmail.com

Key Words: insulin • metabolism • growth factors • atherosclerosis • endothelium

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

Recent advances in cardiology have focused on proliferation and regeneration as potential cardiovascular defense mechanisms. Within this framework, growth factors are acquiring increasing importance; insulin-like growth factor-1 (IGF-1) emerges among them for its versatile pleiotropic actions. This review provides a current perspective on IGF-1 and vascular disease.

I. Insulin-Like Growth Factor-1 and Vascular Disease: Friend or Foe?

The IGF-1 system is dynamic and complex,^1,2 involving at least 6 IGF-1–binding proteins (IGFBP-1 through -6) and several binding protein–related proteases,¹ including pregnancy-associated plasma protein-A (PAPP-A). The latter promotes IGF-1 bioavailability by cleaving IGFBP-4 and -5.³ Acute coronary syndromes have been associated with raised PAPP-A concentrations in blood, leading to the interpretation that PAPP-A may enhance the risk of coronary artery disease through increased IGF-1 in vascular tissues.⁴ Recent results, however, suggest a different relation between IGF-1 and ischemic syndromes.

II. IGF-1: Vascular Detrimental Factor?

Indirect data have supported the concept that IGF-1 may be atherogenetic because it can induce vascular smooth muscle cell (VSMC) proliferation in vitro.⁵ Early studies on VSMCs from human and rabbit atherosclerotic arteries showed enhanced staining for IGF-1 and its receptor^6,7 compared with normal tissues,⁷ with further enhancement after experimental angioplasty.⁷ Thus, IGF-1 has been considered a promoter of arterial obstructive lesions⁸; an alternative possibility, however (consistent with the higher IGF-1 expression after angioplasty), is that IGF-1 initiates a survival pathway aimed at compensating local vascular cell apoptosis (see sections III.C.3 and III.C.4).

Randomized trials of the somatostatin analogue, angiopeptin, have been performed in the setting of postangioplasty restenosis and heart transplant vasculopathy to assess the possible benefits of lowering IGF-1 levels.⁹ . . . [Full Text of this Article]

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