scholarly journals Telmisartan Lowers Elevated Blood Pressure in Psoriatic Mice without Attenuating Vascular Dysfunction and Inflammation

2019 ◽  
Vol 20 (17) ◽  
pp. 4261 ◽  
Author(s):  
Johannes Wild ◽  
Rebecca Schüler ◽  
Tanja Knopp ◽  
Michael Molitor ◽  
Sabine Kossmann ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mouse Model ◽  
Skin Disease ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Skin Inflammation ◽  
Severe Psoriasis ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
The Impact

Background: Psoriasis is hallmarked by vascular dysfunction, arterial hypertension, and an increased risk for cardiovascular diseases. We have shown recently that skin-driven interleukin (IL)-17A expression promotes psoriasis-like disease in mice, and this is associated with vascular inflammation, vascular dysfunction, and hypertension. As an intensive risk-factor reduction is recommended for psoriasis patients, we aimed to elucidate the impact of the angiotensin II receptor type 1 (AT1) antagonist telmisartan in a mouse model of severe psoriasis-like skin disease. Methods and Results: Elevated blood pressure measured by tail-cuff plethysmography in mice with keratinocyte-specific IL-17A overexpression (K14-IL-17Aind/+ mice) was significantly reduced in response to telmisartan. Importantly, vascular dysfunction, as assessed by isometric tension studies of isolated aortic rings, vascular inflammation measured by flow cytometry analysis of CD45+CD11b+ immune cells, as well as the increased peripheral oxidative stress levels assessed by L-012-enhanced chemiluminescence were not attenuated by telmisartan treatment of K14-IL-17Aind/+ mice, nor was the persisting skin inflammation. Conclusion: We provide first evidence for an effective antihypertensive treatment in experimental psoriasis by AT1 blockade, but without any impact on vascular inflammation and dysfunction in our mouse model of severe psoriasis-like skin disease. This suggests that vascular function and inflammation in psoriasis might not be attenuated as long as skin inflammation persists.

scholarly journals 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The role of the mineralocorticoid receptor in the vasculature

2017 ◽  
Vol 234 (1) ◽  
pp. T67-T82 ◽  
Author(s):  
Jennifer J DuPont ◽  
Iris Z Jaffe
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Mineralocorticoid Receptor ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Kidney Injury ◽  
Vascular Pathology ◽  
The Impact

Since the mineralocorticoid receptor (MR) was cloned 30 years ago, it has become clear that MR is expressed in extra-renal tissues, including the cardiovascular system, where it is expressed in all cells of the vasculature. Understanding the role of MR in the vasculature has been of particular interest as clinical trials show that MR antagonism improves cardiovascular outcomes out of proportion to changes in blood pressure. The last 30 years of research have demonstrated that MR is a functional hormone-activated transcription factor in vascular smooth muscle cells and endothelial cells. This review summarizes advances in our understanding of the role of vascular MR in regulating blood pressure and vascular function, and its contribution to vascular disease. Specifically, vascular MR contributes directly to blood pressure control and to vascular dysfunction and remodeling in response to hypertension, obesity and vascular injury. The literature is summarized with respect to the role of vascular MR in conditions including: pulmonary hypertension; cerebral vascular remodeling and stroke; vascular inflammation, atherosclerosis and myocardial infarction; acute kidney injury; and vascular pathology in the eye. Considerations regarding the impact of age and sex on the function of vascular MR are also described. Further investigation of the precise molecular mechanisms by which MR contributes to these processes will aid in the identification of novel therapeutic targets to reduce cardiovascular disease (CVD)-related morbidity and mortality.

Abstract P143: Hypertension and Inflammation-Related microRNAs

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jamie G Hijmans ◽  
Tyler D Bammert ◽  
Philip J Kavlich ◽  
Kyle J Diehl ◽  
Grace M Lincenberg ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Messenger Rna ◽  
Vascular Inflammation ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Cvd Risk ◽  
Significant Group ◽  
Altered Expression ◽  
Inflammatory Stress ◽  
Inflammatory State

microRNAs (miRs) are short single stranded noncoding RNAs that are involved in the regulation of a number of physiological and pathological processes. miRs down regulate target gene expression post-transcriptionally by degrading messenger RNA and/or by blocking translation. It is now recognized that miRs play a key role in regulating inflammation, vascular health and in-turn, cardiovascular disease (CVD). For example, altered expression of specific miRs such as, miR-126, miR-146a and miR-150 have been linked with heightened vascular inflammation and CVD risk. Hypertension is associated with increased inflammatory burden. The mechanisms underlying blood pressure-related inflammatory stress are not fully understood. It is currently unknown whether inflammation-related miRs are dysregulated with elevated blood pressure. Accordingly, the aim of this ongoing study is to determine the influence of hypertension, independent of other risk factors, on circulating expression of miR-34a, miR-92a, miR -126, miR-146a and miR-150. To date, 28 sedentary, middle-aged adults have been studied: 14 normotensive (NT; 12M/2F; age: 53±1 yr; BP: 114/71±2/1 mmHg) and 14 hypertensive (HT; 12M/2F; 56±2 yr; 142/90±2/2 mmHg). All subjects were non-smokers, normolipidemic, non-medicated and free of overt CVD. Circulating expression of miRs was determined in plasma using standard RT-PCR techniques with miR primers of interest. Expression was normalized to exogenous C. elegans miR-39 and reported as relative expression in arbitrary units (AU). Circulating expression of miR-126 (0.14±0.03 vs 0.33±0.04 AU) and miR-150 (0.06±0.02 vs 0.12±0.02 AU) were markedly lower (~135% and 100%, respectively; P<0.05) in the HT vs NT groups. There was no significant group difference in miR-34a (0.017±0.005 vs 0.010±0.001 AU), miR-92a (0.66±0.16 vs 1.01±0.13 AU) and miR-146a (0.04±0.01 vs 0.06±0.01 AU). Lower expression of miR-126 and miR-150 is consistent with a proinflammatory phenotype, as both are involved in limiting inflammatory pathways. In summary, these initial results suggest that dysregulation of key inflammation-related miRs may contribute mechanistically to the heightened inflammatory state associated with elevated blood pressure and deserve further study.

scholarly journals The Impact of Metabolic Syndrome on the Incidence of Atrial Fibrillation: A Nationwide Longitudinal Cohort Study in South Korea

2019 ◽  
Vol 8 (8) ◽  
pp. 1095 ◽  
Author(s):  
Kwon ◽  
Kim ◽  
Kim ◽  
Kim ◽  
Kim ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Abdominal Obesity ◽  
National Health ◽  
Fasting Glucose ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Increased Risk ◽  
The Impact

Aims: To evaluate the impact of metabolic syndrome (MetS) status on the incidence of atrial fibrillation (AF) in Koreans. Methods and results: Data obtained from the Korean National Health Insurance Service from 2009 to 2016 were analyzed. In total, 7,830,602 men and women (between 30 and 69 years of age) without baseline AF who underwent a national health examination between January 2009 and December 2009 were enrolled. Patients were evaluated to determine the impact of MetS status on their risk of developing AF until December 2016. Using the National Cholesterol Education Program Adult Treatment Panel III criteria, patients were placed into one of three groups depending on MetS component numbers: 0 (normal), 1–2 (Pre-MetS) or 3–5 (MetS). During a mean follow-up of 7.3 years, 20,708 subjects (0.26%) were diagnosed with AF. After multivariable adjustment, the risk of AF was significantly and positively correlated with MetS status (hazard ratios (HR) 1.391, 95% confidence interval (CI) 1.322–1.464 in Pre-MetS and HR 1.722, 95% CI 1.621–1.829 in MetS). When subgroup analyses were conducted according to MetS components, abdominal obesity (HR 1.316, p < 0.001), elevated blood pressure (HR 1.451, p < 0.001), and elevated fasting glucose (HR 1.163, p < 0.001) were associated with an increased risk of AF. Conclusion: MetS and pre-MetS are significantly associated with an increased risk of AF in Korean adults. Of the MetS components, abdominal obesity, elevated blood pressure, and elevated fasting glucose are potent risk factors for the risk of AF in this population.

Mechanisms underlying developmental programming of elevated blood pressure and vascular dysfunction: evidence from human studies and experimental animal models

2007 ◽  
Vol 114 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Anne Monique Nuyt
Keyword(s):  
Blood Pressure ◽  
Vascular Dysfunction ◽  
Renin Angiotensin System ◽  
Later Life ◽  
Epidemiological Studies ◽  
Experimental Models ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Early Life Conditions

Cardiovascular-related diseases are the leading cause of death in the world in both men and women. In addition to the environmental and genetic factors, early life conditions are now also considered important contributing elements to these pathologies. The concept of ‘fetal’ or ‘developmental’ origins of adult diseases has received increased recognition over the last decade, yet the mechanism by which altered perinatal environment can lead to dysfunction mostly apparent in the adult are incompletely understood. This review will focus on the mechanisms and pathways that epidemiological studies and experimental models have revealed underlying the adult cardiovascular phenotype dictated by the perinatal experience, as well as the probable key causal or triggering elements. Programmed elevated blood pressure in the adult human or animal is characterized by vascular dysfunction and microvascular rarefaction. Developmental mechanisms that have been more extensively studied include glucocorticoid exposure, the role of the kidneys and the renin–angiotensin system. Other pathophysiological pathways have been explored, such as the role of the brain and the sympathetic nervous system, oxidative stress and epigenetic changes. As with many complex diseases, a unifying hypothesis linking the perinatal environment to elevated blood pressure and vascular dysfunction in later life cannot be presumed, and a better understanding of those mechanisms is critical before clinical trials of preventive or ‘deprogramming’ measures can be designed.

scholarly journals Inflammatory Skin-Derived Cytokines Accelerate Osteoporosis in Mice with Persistent Skin Inflammation

2020 ◽  
Vol 21 (10) ◽  
pp. 3620 ◽  
Author(s):  
Kento Mizutani ◽  
Kana Isono ◽  
Yoshiaki Matsushima ◽  
Karin Okada ◽  
Ai Umaoka ◽  
...  
Keyword(s):  
Blood Flow ◽  
Bone Density ◽  
Mouse Model ◽  
Skin Disease ◽  
Bone Structure ◽  
Skin Inflammation ◽  
Inflammatory Skin Disease ◽  
Inflammatory Skin ◽  
Skin Conditions ◽  
The Impact

Secondary osteoporosis can also be caused by chronic inflammatory skin disease as well as rheumatoid arthritis or inflammatory bowel disease. However, the exact role of osteoporosis in inflammatory skin conditions has not been elucidated. Using a mouse model of dermatitis, we investigated the pathophysiology of osteoporosis in inflammatory skin conditions and the therapeutic impact of osteoporosis medication on inflammatory skin disease. We employed model mice of spontaneous skin inflammation, specifically overexpressing human caspase-1 in the epidermis. Bone density and the expression of various mRNAs in the femur were examined by micro CT and RT-PCR. The effects of minodronate and anti-RANKL antibody on bone structure, histology, and femur blood flow were studied. The mouse model of skin inflammation showed a marked decrease in bone density compared to wild-type littermates with abnormalities in both bone resorption and formation. Minodronate improved bone density by decreasing osteoclasts, but anti-RANKL antibody did not improve. In the dermatitis model, the blood flow in the bone marrow was decreased, and minodronate restored this parameter. A model of persistent dermatitis exhibited marked osteoporosis, but the impact of chronic dermatitis on osteoporosis has not been thoroughly investigated. We should explore the pathogenesis of osteoporosis in skin inflammatory diseases.

The impact of elevated blood pressure on exercise capacity in elite athletes

2015 ◽  
Vol 180 ◽  
pp. 171-177 ◽  
Author(s):  
Sanja Mazic ◽  
Jelena Suzic Lazic ◽  
Milica Dekleva ◽  
Milena Antic ◽  
Ivan Soldatovic ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Exercise Capacity ◽  
Elite Athletes ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
The Impact

Obesity-Related Parameters Are Associated With Blood Pressure in Palestinian Children

2020 ◽  
pp. 109980042094107
Author(s):  
Moath Abu Ejheisheh ◽  
María Correa-Rodríguez ◽  
Ángel Fernández-Aparicio ◽  
Ahmad Batran ◽  
María José Membrive-Jiménez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Composition ◽  
Diastolic Blood Pressure ◽  
Fat Mass ◽  
Fat Free Mass ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Elevated Systolic Blood Pressure ◽  
Palestinian Children ◽  
The Impact

Hypertension has been established as a common health condition in young people. Most studies have focused on the impact of body mass index (BMI), but the relationships between body composition parameters and blood pressure in Palestinian children has not previously been investigated. We aimed to analyze the prevalence of overweight/obesity and elevated blood pressure/hypertension and investigate the associations among obesity-related parameters, including anthropometric and body composition markers and blood pressure levels in a population of 971 Palestinian school children (50% girls; mean age 10.3 ± 1.1 years). Anthropometric measurements including height, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), and waist to height ratio (WHtR) were assessed. A body composition analyzer was used to measure body weight, fat mass, and fat-free mass. Blood pressure including systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) were measured using a Dinamap vital signs monitor. The prevalence of overweight/obesity was 25.3% in the girls and 23.1% in the boys. 26.3% of the children had elevated systolic blood pressure, or systolic hypertension; whereas 23.4% had elevated diastolic blood pressure, or diastolic hypertension. All obesity-related variables, with the exception of WHR and WHtR, showed statistical differences among the normotension, elevated blood pressure and hypertension groups for systolic and diastolic blood pressure ( p < 0.05). Children with elevated blood pressure or hypertension had significantly higher weight, BMI, WC, HC, fat mass, and fat-free mass values compared to participants with normotension, supporting the direct association between obesity and hypertension in this population. Weight-reduction interventions are essential for reducing the prevalence of childhood hypertension in Palestinian children.

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