Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension.

Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. Abstract Text:

OBJECTIVES: Arterial stiffening and endothelial dysfunction are hallmarks of aging, and advanced glycation endproducts (AGE) may contribute to these changes. We tested the hypothesis that AGE crosslink breakers enhance endothelial flow-mediated dilation (FMD) in humans and examined the potential mechanisms for this effect. METHODS: Thirteen adults (nine men, aged 65 +/- 2 years) with isolated systolic hypertension (systolic blood pressure > 140 mmHg, diastolic blood pressure < 90 mmHg or pulse pressure > 60 mmHg) on stable antihypertensive therapy were studied. Subjects received placebo (2 weeks) then oral alagebrium (ALT-711; 210 mg twice a day for 8 weeks). Subjects and data analyses were blinded to treatment. Arterial stiffness was assessed by carotid augmentation index (AI) and brachial artery distensibility (ArtD) using applanation tonometry and Doppler echo, and endothelial function by brachial FMD. Serum markers of collagen metabolism and vascular inflammation were assessed. RESULTS: Alagebrium reduced carotid AI by 37% (P = 0.007) and augmented pressure (16.4 +/- 10 to 9.6 +/- 9 mmHg; P < 0.001). Heart rate, arterial pressures, and ArtD, were unchanged. FMD increased from 4.6 +/- 1.1 to 7.1 +/- 1.1% with alagebrium (P < 0.05), and was unrelated to altered shear stress or regional arterial distensibility. However, FMD change was inversely related to markers of collagen synthesis, p-selectin and intracellular cell adhesion molecule (all P < 0.05). Alagebrium-associated changes in plasma nitrite plus nitrate was inversely correlated with plasma matrix metalloproteinase 9 and type I collagen (P = 0.007). CONCLUSIONS: Alagebrium enhances peripheral artery endothelial function and improves overall impedance matching. Improved endothelial function correlates better with reduced vascular fibrosis and inflammation markers than with vessel distensibility. AGE-crosslink breakers may reduce cardiovascular risk in older adults by reduced central arterial stiffness and vascular remodeling.

Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. Publishing Authors By Initials

For similar vasodilation research abstracts see: vasodilation research

PUBMED ID PMID:

MEDLINE DATE:

Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of hypertension

VOLUME: 25

Page Numbers: 577-83

Journal Abbreviation: J. Hypertens.

ISSN: 0263-6352

DAY: 3

MONTH: Mar

YEAR: 2007

Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8306882

Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. Keywords Mesh Terms:

KEYWORDS: Vasodilation

MESH TERMS: physiology

Chemical & Substance for Abstract: Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. Information

Substance Name: Matrix Metalloproteinase 9

Registry Number: EC 3.4.24.35

Grant and Affiliation Information for Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension.

AFFILIATION: Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. azieman@jhmi.edu

Country: England

AGENCY: United States NIA

GRANT: AG-18324

ACRONYM: AG

MEDLINETA: J Hypertens

REFSOURCE: J Hypertens. 2007 Mar;25(3):509-10

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Advanced glycation endproduct crosslink breaker alagebrium improves endothelial function in patients with isolated systolic hypertension Related Publications

• A colorimetric microanalytical method for acetate and fluoroacetate.
• Adrenergic regulation of a key cardiac potassium channel can contribute to atrial fibrillation: evidence from an IKs transgenic mouse.
• Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension.
• Altered Na+ channels promote pause-induced spontaneous diastolic activity in long QT syndrome type 3 myocytes.
• An epidemic of dyssynchrony: but what does it mean?
• Assessment of the ethical review process in Sudan.
• Comparison of direct immunofluorescence, immunoassays, and fecal flotation for detection of Cryptosporidium spp. and Giardia spp. in naturally exposed cats in 4 Northern California animal shelters.
• Comparison of initial intraocular pressure response with topical beta-adrenergic antagonists and prostaglandin analogues in African American and white individuals in the Ocular Hypertension Treatment Study.
• Comparison of ophthalmic measurements obtained via high-frequency ultrasound imaging in four species of snakes.
• Control of in vivo contraction/relaxation kinetics by myosin binding protein C: protein kinase a phosphorylation dependent and independent regulation.
• Coverage-adjusted entropy estimation.
• Determination of the in vitro susceptibility of feline tritrichomonas foetus to 5 antimicrobial agents.
• Estimation of central pressure augmentation using automated radial artery tonometry.
• Fading sodium channels in failing hearts.
• Hydrogen-deuterium exchange and selective labeling of deprotonated amino acids and peptides in the gas phase.
• Impact of arterial load and loading sequence on left ventricular tissue velocities in humans.
• Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction.
• In vitro methylation of predetermined regions in recombinant DNA constructs.
• Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of action.
• Mutation of an A-kinase-anchoring protein causes long-QT syndrome.
• Pathology partnerships that save lives worldwide.
• Recent integrations of mammalian Hmg retropseudogenes.
• Reversing chronic remodeling in heart failure.
• Semi-automated data processing of hydrogen exchange mass spectra using HX-Express.
• Shear stress inhibition of H(2)O (2) induced p66 (Shc) phosphorylation by ASK1-JNK inactivation in endothelium.
• Small-molecule therapies for cardiac hypertrophy: moving beneath the cell surface.
• Therapeutic potential of tetrahydrobiopterin for treating vascular and cardiac disease.
• Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension.
• Wechsler's mental deterioration index in the diagnosis of organic brain disease.
• Zwitterion-dianion complexes and anion-anion clusters with negative dissociation energies.