Anti-VCAM1 monoclonal antibody, clone 435

Objective: Systemic inflammation and impaired function of endothelium play an important role in the development of hypertension. Our study aimed to analyze an association between essential hypertension and polymorphic markers in candidate genes in the group of 530 Tatars from the Republic of Bashkortostan, Russia. Methods: The study group consisted of 216 male patients with essential hypertension (mean age 48.928.8 years) and 314 healthy individuals of corresponding sex and age without history of cardiovascular disease. Association between studied polymorphisms and essential hypertension was analyzed using PLINK. Results: We detected an association between EDNRB rs5351, VEGFA -2549(18)I/D, and ADRB2 rs1042713 polymorphisms and essential hypertension in men of Tatar ethnic origin. EDNRB, VEGFA, and VCAM1 single-nucleotide polymorphisms were associated with SBP and DBP. However, only EDNRB rs5351 remained associated with hypertension after Bonferroni correction for multiple testing. A Markov chain Monte Carlo-based approach implemented in the APSampler program was used to analyze association of genotype and/or allele combinations with disease. The most influential in conferring risk of hypertension was EDNRBG/G+ADRB2A+VCAM1A combination (odds ratio=4.15, P-Bonf=5.43x10(-8)). Conclusion: Our results suggest that rs5351 single-nucleotide polymorphism is a strong independent predictor of essential hypertension in men of Tatar ethnic origin.

Liposomes may be engineered to target inflamed endothelium by mimicking ligand receptor interactions between leukocytes and cytokine-activated endothelial cells (ECs). The upregulation and assembly of vascular cell adhesion molecule-1 (VCAM1) and E-selectin on the cell membrane upon exposure to cytokines have shown potential for drug delivery vehicles to target sites of chronic endothelial inflammation, such as atherosclerosis and cancer. Herein, we characterized EC surfaces by measuring the E-selectin and VCAM1 surface densities and adhesion forces of aVCAM1 and aE-selectin to ECs. We quantified the antibody density, ratio, and diffusivity of liposomes to achieve significant binding and internalization. At 1 h, the 1:1 ratio of VCAM1:E-selectin antibodies was significantly higher than 1:0 and 0:1. Significant binding and uptake was achieved at aE-selectin densities as low as 400 molecules/gm(2). The highest levels of binding and uptake were achieved when using a 1:1 ratio of VCAM1:E-selectin antibodies at a density of 1000 molecules/mu m(2); this density is 85% lower than previous reports. The binding and uptake of functionalized liposomes were reduced to levels comparable to IgG functionalized liposomes upon a 10-fold reduction in liposome membrane diffusivity. We conclude with a liposomal design that discriminates between healthy and inflamed endothelium while reducing antibody surface presentation. (C) 2014 Elsevier Ltd. All rights reserved.