scholarly journals Cardiovascular Damage Associated With Chest Irradiation

2020 ◽  
Vol 7 ◽  
Author(s):  
Simone M. Mrotzek ◽  
Tienush Rassaf ◽  
Matthias Totzeck
Keyword(s):  
Cardiovascular Damage ◽  
Chest Irradiation

Abstract 74: The Nox4 Inhibitor GKT137831, Prevents Aldosterone Production by Adipocytes and Protects Against Adipose Tissue Inflammation and Fibrosis in Obese Mice

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Sarah Even ◽  
Aurelie Nguyen Dinh Cat ◽  
Francisco J Rios ◽  
Antunes T Tayze ◽  
Ying He ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Culture Media ◽  
Inflammatory Marker ◽  
High Dose ◽  
Obese Mice ◽  
Cardiovascular Damage ◽  
Aldosterone Production ◽  
Inflammatory Phenotype ◽  
Sirius Red

Aldosterone (aldo) plays an important role in obesity-associated cardiovascular risk. We demonstrated that aldo is produced by adipocytes, an effect associated with increased generation of reactive oxygen species (ROS). These processes are exaggerated in obesity. The relationship between adipocyte aldosterone and ROS is unclear. We postulated that Nox4-derived ROS is important for aldo production in adipocytes and leads to a pro-inflammatory phenotype in obesity. Studies were performed in db/m (lean) and db/db (obese) mice, treated with low (20mg/kg/day) or high dose (60mg/kg/day) GKT137831 (GKT, Nox4 inhibitor, 16 weeks). Epididymal (EVAT) and perivascular (PVAT) fat were collected. Plasma and adipocyte aldo were measured by ELISA. Adipose tissue fibrosis was evaluated by picro Sirius red staining and inflammatory mediators by immunostudies. Body weight was increased in db/db mice (61.8g vs control 33.5g), with no effect of GKT. Epididymal adiposity was increased in db/db mice (0.098g vs. 0.067g, p<0.05). Plasma aldo levels in db/db (pg/mL: 518 vs. 272g) and aldo levels in culture media from db/db adipocytes were increased (pg/mL/μg RNA: 1964 vs. 388), p<0.05. All effects decreased by high dose GKT. In PVAT, CYP11B2 gene expression was increased in db/db (2.6±0.8 vs control 1.1±0.1, p<0.05), an effect blocked by Nox4 inhibition. Gene expression of adipocyte differentiation marker, AP2, was increased (3.5±1.1 vs control 1.4±0.4) while anti-inflammatory marker adiponectin was decreased (0.7±0.1 vs control 1.3±0.2, p<0.05)) in obese mice. GKT decreased AP2 levels. Adipocyte-derived TNFα was increased in db/db (4.9±1.8 vs control 1.6±0.6, p<0.05), an effect blocked by GKT. Pro-collagen I, marker of fibrosis, was increased in db/db mice (132±11 vs control 87±4, p<0.05). Sirius red staining was exaggerated in EVAT from db/db mice, and decreased by Nox4 inhibition. In conclusion, Nox4 plays a role in regulating adipocyte-derived aldosterone and promotes a pro-inflammatory and profibrotic adipose phenotype in obese db/db mice. These findings suggest that adipocyte Nox4 links hyperaldosteronism and inflammation/fibrosis in adiposity and as such may be a putative therapeutic target for obesity-associated cardiovascular damage.

scholarly journals Microbiota metabolites: Pivotal players of cardiovascular damage in chronic kidney disease

2018 ◽  
Vol 130 ◽  
pp. 132-142 ◽  
Author(s):  
Carmela Cosola ◽  
Maria Teresa Rocchetti ◽  
Adamasco Cupisti ◽  
Loreto Gesualdo
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiovascular Damage

Mechanisms contributing to cardiac remodelling

2017 ◽  
Vol 131 (18) ◽  
pp. 2319-2345 ◽  
Author(s):  
Qing-Qing Wu ◽  
Yang Xiao ◽  
Yuan Yuan ◽  
Zhen-Guo Ma ◽  
Hai-Han Liao ◽  
...  
Keyword(s):  
Cellular Responses ◽  
Cardiac Remodelling ◽  
Signalling Pathways ◽  
Neurohormonal Activation ◽  
Functional Changes ◽  
Biomechanical Stress ◽  
Cardiovascular Damage ◽  
Ischaemia Reperfusion ◽  
Clinical Heart Failure ◽  
Cellular Dysfunction

Cardiac remodelling is classified as physiological (in response to growth, exercise and pregnancy) or pathological (in response to inflammation, ischaemia, ischaemia/reperfusion (I/R) injury, biomechanical stress, excess neurohormonal activation and excess afterload). Physiological remodelling of the heart is characterized by a fine-tuned and orchestrated process of beneficial adaptations. Pathological cardiac remodelling is the process of structural and functional changes in the left ventricle (LV) in response to internal or external cardiovascular damage or influence by pathogenic risk factors, and is a precursor of clinical heart failure (HF). Pathological remodelling is associated with fibrosis, inflammation and cellular dysfunction (e.g. abnormal cardiomyocyte/non-cardiomyocyte interactions, oxidative stress, endoplasmic reticulum (ER) stress, autophagy alterations, impairment of metabolism and signalling pathways), leading to HF. This review describes the key molecular and cellular responses involved in pathological cardiac remodelling.

scholarly journals The Role of Endothelial Dysfunction in the Pathogenesis of Vascular Complications of Diabetes Mellitus - A High Priority Area of Investigation

2015 ◽  
Vol 22 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Rodica Teodora Străchinariu
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Vascular Complications ◽  
Noninvasive Methods ◽  
Cardiovascular Damage ◽  
Vasoactive Substances ◽  
Organ Systems ◽  
Increased Risk

Abstract Endothelium, the inner layer of the vasculature, represents the interface between blood and organ systems and it is active in the process of contraction and relaxation of vascular smooth muscle and in functions like secretion of vasoactive substances. Endothelial dysfunction is an important cause of cardiovascular disease. The function of the endothelium can be assessed by invasive and noninvasive methods. Endothelial cells produce vasoactive substances like endothelium derived relaxing factor, prostacyclin, nitric oxide, and endothelium derived hyperpolarizing factor. Diabetes mellitus is associated with an increased risk of cardiovascular diseases. Hyperglycemia leads to cardiovascular damage through different pathways, including the polyol and hexosamine pathways, generation of advanced glycation end products, and activation of protein kinase C. Together with hyperglycemia induced mitochondrial dysfunction and endoplasmic reticulum stress, all these can promote the accumulation of reactive oxygen species. The oxidative stress induced by hyperglycemia promotes endothelial dysfunction with an important role in micro and macro vascular disease. Insulin-resistance could be independently predictive of cardiovascular disease. Life style modification and pharmacotherapy could possibly ameliorate the effect of insulin resistance

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