Fibrillar proteins, such as collagens type I and III, and elastin are components of the extracellular matrix. They form an intricate widespread network that provides a basis for maintaining the physical structure of the heart and vessels and also play an important role in determining cardiovascular function. Physiologically, collagen and elastin fibres are enzymatically cross-linked to form matrix. In addition to these enzymatically formed cross-links, collagen fibres may be linked non-enzymatically, most notably by formation of AGEs (advanced glycation end-products). AGEs are formed by a reaction between reducing sugars and body proteins; they are formed increasingly in diabetes mellitus and hypertension and they accumulate with aging. There are several mechanisms whereby AGEs may affect cardiovascular structure and function. These include increased myocardial and vascular stiffness and (upon reaction with their receptors) inflammatory reactions, release of growth factors and cytokines, and increased oxidative stress. Therefore breaking AGEs appears as a promising tool in the therapy of cardiovascular injury related to diabetes, hypertension and aging. Breakers of AGE cross-links have been developed and one of them, alagebrium, has been extensively studied. This brief review discusses the formation of AGEs, their role in mediating cardiovascular injury, as well as the results of experimental and clinical studies involving alagebrium.
Skip Nav Destination
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article| October 25 2007
Cross-link breakers as a new therapeutic approach to cardiovascular disease
D. Susic 1
1Hypertension Research Laboratory, Division of Research, Ochsner Clinic Foundation, 1520 Jefferson Highway, New Orleans, LA 70121, U.S.A.
Search for other works by this author on:
Biochem Soc Trans (2007) 35 (5): 853–856.
June 11 2007
D. Susic; Cross-link breakers as a new therapeutic approach to cardiovascular disease. Biochem Soc Trans 1 November 2007; 35 (5): 853–856. doi: https://doi.org/10.1042/BST0350853
Download citation file:
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your InstitutionSign in via your Institution
Get Access To This Article
Buy This Article