BACKGROUND Despite its high prevalence, optimal therapy for diastolic heart failure (DHF) has not been determined. Alagebrium chloride (ALT-711) is a novel compound that breaks glucose crosslinks and may improve ventricular and arterial compliance. METHODS AND RESULTS A total of 23 patients, mean age 71 years, with stable DHF, ejection fraction (EF) >50%, were enrolled in a 16-week, open-labe...

Pressure-induced vasodilation, a neurovascular mechanism relying on the interaction between mechanosensitive C-fibers and vessels, allows skin blood flow to increase in response to locally nonnociceptive applied pressure that in turn may protect against pressure ulcers. We expected that severe neuropathy would dramatically affect pressure-induced vasodilation in diabetic mice, and we aimed to d...

Advanced-glycation end products (AGEs) were recently implicated in vascular calcification, through a process mediated by RAGE (receptor for AGEs). Although a correlation between AGEs levels and vascular calcification was established, there is no evidence that reducing in vivo AGEs deposition or inhibiting AGEs-RAGE signaling pathways can decrease medial calcification. We evaluated the impact of...

A diet high in fat induces cardiac hypertrophy, inflammation, and oxidative stress. Although such actions have largely been ascribed to fat deposition, the accumulation of advanced glycation end products (AGEs) and subsequent activation of the receptor for AGEs (RAGE) may also represent important mediators of cardiac injury following exposure to a Western diet. In this study, male C57BL6J and R...

Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain ...

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 mat...

OBJECTIVE Pressure-induced vasodilation (PIV) allows skin blood flow to increase in response to locally applied pressure and may be protective against pressure ulcers. We previously showed that PIV was absent in 1-week diabetic mice exhibiting no neuropathy. Our aim was to determine whether the diabetes-induced PIV alteration could be prevented. METHODS AND RESULTS Diabetic mice received no t...

Although the features of diabetic cardiomyopathy, atherosclerosis, and nephropathy have been clinically characterized, the pathogenesis and the mechanisms underlying the abnormalities in the diabetic heart and kidney are not fully understood. During the past several years, in an attempt to discover interventions for diabetes-related complications, researchers have refocused their attention from...