Cardiovascular

Diabetic patients have elevated serum and tissue levels of A.G.E.s that are associated with an elevated risk of atherosclerotic disease. Preclinical studies using crosslink breakers developed at Synvista suggest that these compounds may elicit profound beneficial effects on the development of atherosclerosis. A.G.E. crosslink breakers such as alagebrium have been shown to restore tissue flexibility and may be useful in the treatment of diastolic heart failure. Synvista is currently conducting clinical trials in diastolic heart failure and diabetic nephropathy.

The Treatment of Heart Failure with Preserved Ejection Fraction ("Diastolic Heart Failure")
Author: Hogg and McMurray
Source: Heart Fail Rev (2006) 11:141–146

Heart Failure and Nephropathy: Catastrophic and Interrelated Complications of Diabetes
Author: Gilbert, et al
Source: Clin J Am Soc Nephrol 1: 2006.

Molecular Basis of Angiopathy in Diabetes Mellitus
Author: Silvestre and Levy
Source: Circ Res. 2006;98:4-6.

C16, a Novel Advanced Glycation Endproduct Breaker, Restores Cardiovascular Dysfunction in Experimental Diabetic Rats¹
Author: Cheng, et al.
Source: Acta Pharmacologica Sinica 2005 Dec; 26 (12): 1460–1466

The Effect of Alagebrium Chloride (ALT-711), a Novel Glucose Cross-Link Breaker, in the Treatment of Elderly Patients With Diastolic Heart Failure
Author: Little, et al.
Source: Journal of Cardiac Failure Vol. 11 No. 3 2005

Importance of Advanced Glycation End Products in Diabetes-Associated Cardiovascular and Renal Disease
Author: Cooper
Source: American Journal of Hypertension, 17:31S–38S, August 2004

Advanced Glycation End Product Interventions Reduce Diabetes-Accelerated Atherosclerosis
Author: Forbes, et al.
Source: Diabetes, Vol. 53, July 2004

Diastolic Heart Failure — Abnormalities in Active Relaxation and Passive Stiffness of the Left Ventricle
Author: Zile, et al.
Source: New England Journal of Medicine, 350;19, May 6, 2004

Understanding "Diastolic" Heart Failure
Author: Redfield
Source: New England Journal of Medicine, 350;19, May 6, 2004

Advanced Glycation End Product Cross-Linking: Pathophysiologic Role and Therapeutic Target in Cardiovascular Disease
Author: Zieman and Kass
Source: Congestive Heart Failure,10:144–151, May-June 2004

Hypertensive Myocardial Fibrosis and Diastolic Dysfunction: Another Model of Inflammation?
Author: Kuwahara F, et al
Source: Hypertension, April 2004

Advanced Glycation Endproduct Crosslinking in the Cardiovascular System
Author: Zieman and Kass
Source: Drugs 2004, 64 (5): 459-470

Crosslink Breakers: A New Approach to Cardiovascular Therapy
Author: Susic, et al.
Source: Current Opinion in Cardiology 2004, 19:336–340

Heart Failure With Preserved Left Ventricular Systolic Function
Author: Hogg, et al.
Source: Journal of the American College of Cardiology, Vol. 43, No. 3, 2004

Increased Central Artery Stiffness in Impaired Glucose Metabolism and Type 2 Diabetes
Author: Schram, et al.
Source: Hypertension, 2004, 43:176-181

What Mechanisms Underlie Diastolic Dysfunction in Heart Failure?
Author: Kass, et al.
Source: Circulation Research, 94:1533-1542, 2004

Effect of ALT-711, A Novel Glucose Crosslink Breaker, on Diastolic Heart Failure
Author: Kitzman, et al.
Source: Wake Forest University Baptist Medical Center, September 3, 2003

Diastolic Heart Failure: Old Story, New Concepts
Author: Mercadier
Source: Archives des Maladies du Coeur et des Vaisseaux, Tome 96, n° 9, Septembre 2003

A Breaker of Advanced Glycation End Products Attenuates Diabetes-Induced Myocardial Structural Changes
Author: Candido, et al.
Source: Circulation Research, 2003, 92:785-792

Arterial Stiffness Increases With Deteriorating Glucose Tolerance Status
Author: Henry, et al.
Source: Circulation, 2003, 107:2089-2095

Biomarkers of Vascular Disease Linking Inflammation to Endothelial Activation, Part II
Author: Szmitko, et al.
Source: Circulation, 2003, 108:2041-2048

Glycated Collagen Cross-Linking Alters Cardiac Mechanics in Volume-Overload Hypertrophy
Author: Herrmann, et al.
Source: American Journal Physiology - Heart and Circulatory Physiology, 2003, 284: H1277–H1284

Glycation End-Product Cross-Link Breaker Reduces Collagen and Improves Cardiac Function in Aging Diabetic Heart
Author: Liu, et al.
Source: American Journal Physiology - Heart and Circulatory Physiology, 2003, 285: H2587-H2591

The Receptor RAGE as a Progression Factor Amplifying Arachidonate-Dependent Inflammatory and Proteolytic Response in Human Atherosclerotic Plaques
Author: Cipollone, et al.
Source: Circulation, 2003, 108:1070-1077

Preferential Stiffening of Central Over Peripheral Arteries in Type 2 Diabetes
Author: Kimoto E, et al
Source: Diabetes, February 2003

Pathophysiological Characterization of Isolated Diastolic Heart Failure in Comparison to Systolic Heart Failure
Author: Kitzman DW, et al
Source: Journal of American Medical Association (JAMA), November 2002

Diastolic Heart Failure in the Elderly
Author: Kitzman DW
Source: Heart Failure Reviews, July 2002

Angiotensin II Receptor Antagonists and Angiotensin- Converting Enzyme Inhibitors Lower In Vitro the Formation of Advanced Glycation End Products: Biochemical Mechanisms
Author: Miyata, et al.
Source: Journal of the American Society of Nephrology, 2002, 13:2478–2487

Diabetes and Cardiovascular Disease - Writing Group II: Pathogenesis of Atherosclerosis in Diabetes
Author: Eckel, et al.
Source: Circulation, 2002, 105:e138-e143

Diabetic Macrovascular Disease - The Glucose Paradox?
Author: Libby and Plutzky
Source: Circulation, 2002, 106:2760-2763

Sugar and Cardiovascular Disease: A Statement for Healthcare Professionals From the Committee on Nutrition of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association
Author: Howard and Wylie-Rosett
Source: Circulation, 2002, 106:523-527

ALT-711, A Collagen Cross-link Breaker, Decreases Myocardial Fibrosis and Improves Endothelial Dysfunction in Hypertensive Dahl Salt Rats
Author: Veronsi M, et al
Source: Presented at the American Heart Association’s 55th Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure, September 2001

A Cross-Link Breaker Has Sustained Effects on Arterial and Ventricular Properties in Older Rhesus Monkeys
Author: Vaitkevicius, et al.
Source: Proceedings of the National Academy of Sciences, USA, Vol. 98, No. 3, January 30, 2001

Aminoguanidine and Aortic Wall Mechanics, Structure, and Composition in Aged Rats
Author: Cantini, et al.
Source: Hypertension, 2001, 38:943-948

Improved Arterial Compliance by a Novel Advanced Glycation End-Product Crosslink Breaker
Author: Kass, et al.
Source: Circulation, 2001, 104:1464-1470

Serum Levels of Advanced Glycation End Products Are Associated With Left Ventricular Diastolic Function in Patients With Type 1 Diabetes
Author: Berg, et al
Source: Diabetes Care, Vol. 22, No. 7, July 1999

Breakers of Advanced Glycation End Products Restore Large Artery Properties in Experimental Diabetes
Author: Wolffenbuttel, et al.
Source: Proceedings of the National Academy of Sciences, USA, Vol. 95, 4630–4634, April 1998

Cardiovascular and Renal Effects of a Collagen Cross-Link Breaker, ALT 711, in Adult and Aged Spontaneously Hypertensive Rats
Author: Susic, et al.
Source: American Journal of Hypertension, 2004, Vol. 17, 328-333