Abstract 665: Hypertension Is Associated With Phenotypic Changes Of Peripheral Blood Monocytes.

Abstract

While immunopathogenesis of atherosclerosis is well defined, immunological mechanisms of hypertension (HTN) and its link to atherosclerosis remain unclear. We hypothesized, that primary HTN is associated with a pro-inflammatory and pro-atherogenic phenotype of circulating monocytes, characterized by co-expression of the Fc-gamma receptor (CD16+) and LPS receptor (CD14+high). Methods: 132 subjects (74M and 58F) with typical clinical risk factors of atherosclerosis were studied. HTN (85%) was diagnosed based on blood pressure monitoring and use of anti-HTN drugs. Monocyte characteristics in the peripheral blood were determined by flow cytometry and plasma cytokine levels by ELISA. Results: CD16+CD14+ cells were more prevalent in subjects with HTN and were highest in subjects whose blood pressure was poorly controlled (Figure ). A significant correlation between blood pressure levels at the time of study (JNC7) and prevalence of CD14+CD16+ monocytes was found (Figure ). These relationships remained significant in multi-variate analysis (p = 0.01; type 3 sum of squares ANOVA) taking into account other major risk factors for atherosclerosis or treatments. Further analysis of subpopulations showed that levels of CD16 +CD14+ (high) monocytes, rather than CD16 + CD14(dim) revealed a strong relationship to hypertension. These monocytes showed significantly higher expression of activation markers HLA-DR and CD45RA and TNF-α production(p<0.05). These results provide a novel marker of inflammation in hypertension and may provide a link between hypertension and the development of atherosclerosis, which has been clinically well defined, but mechanistically unclear.

Modulation of nitric oxide by flavonoids

“…6 A mitochondrial NOS isoform (mtNOS) has been under debate, however recent evidence supports the notion that mtNOS is mostly a variant of nNOS. An excessive and sustained production of NO by iNOS has been associated with the pathogenesis of septic shock and inammatory diseases, 22,23 while a decrease in the NO production by eNOS in the vasculature leads to endothelial dysfunction. 6 Therefore, modulation of inducible and constitutive NO production is an important pharmacological target.…”

“…Cell and tissue damage by the NO radical itself or ONOO À contribute to the pathogenesis of septic shock and inammatory-related diseases including Alzheimer, cardiovascular diseases, diabetes and cancer. 22,23 Compounds able to reduce iNOS-derived NO may be thus attractive anti-inammatory agents. For this reason, the effects of plant avonoids on iNOS expression and/ or activity have been extensively studied, using in vitro models of inammation.…”

“…An overproduction of NO from iNOS has been associated with the pathogenesis of septic shock and inammatory diseases. 22,23 Neuroinammation. Sustained neuroinammation processes may contribute to the cascade of events culminating in the progressive neuronal damage observed in many neurodegenerative disorders, most notably Parkinson's disease and Alzheimer's disease, and also with neuronal injury associated with the stroke.…”

The hydroxy-analogue of selenomethionine alleviated lipopolysaccharide-induced inflammatory responses is associated with recover expression of several selenoprotein encoding genes in the spleens of Kunming mice

“…Inflammation is a response of an organism to injury caused by physical or chemical noxious stimuli or microbiological toxins, 1 such as heavy metal-caused inflammation in chickens. 2,3 Inflammatory response is a defensive reaction that helps the body to inactivate or destroy invading organisms, remove irritants, and set the stage for tissue repair.…”

Purification of eleutherosides by macroporous resin and the active fractions of anti-inflammatory and antioxidant activity from Acanthopanax senticosus extract

“…Excess NO production has been implicated in inammatory diseases, such as septic shock and autoimmune diseases. 20 Therefore, inhibition of NO production has been identied as a promising therapy for the treatment of inammatory diseases. 21 Now, Acanthopanax senticosus is a popular medicinal plant that is used in the daily diet and the antioxidant potency and the anti-inammatory effects of its extracts has been widely investigated.…”