Background-Hypertensive target organ damage, especially cardiac hypertrophy with heart failure and arrhythmia, is a major source of morbidity and mortality. Angiotensin II, a major mediator of hypertension and cardiac damage, has proinflammatory properties. Inflammation and activation of the immune system play a pivotal role in pathogenesis of hypertensive target organ damage. However, the role of immunosuppressive CD4
Abstract-We compared the effect n-3 polyunsaturated fatty acids (PUFAs) with direct renin inhibition on electrophysiological remodeling in angiotensin II-induced cardiac injury. We treated double-transgenic rats expressing the human renin and angiotensinogen genes (dTGRs) from week 4 to 7 with n-3 PUFA ethyl-esters (Omacor; 25-g/kg diet) or a direct renin inhibitor (aliskiren; 3 mg/kg per day). Sprague-Dawley rats were controls. We performed electrocardiographic, magnetocardiographic, and programmed electrical stimulation. Dietary n-3 PUFAs increased the cardiac content of eicosapentaenoic and docosahexaenoic acid. At week 7, mortality in dTGRs was 31%, whereas none of the n-3 PUFA-or aliskiren-treated dTGRs died. Systolic blood pressure was modestly reduced in n-3 PUFA-treated (180Ϯ3 mm Hg) compared with dTGRs (208Ϯ5 mm Hg). Aliskiren-treated dTGRs and SpragueDawley rats were normotensive (110Ϯ3 and 119Ϯ6 mm Hg, respectively). Both n-3 PUFA-treated and untreated dTGRs showed cardiac hypertrophy and increased atrial natriuretic peptide levels. Prolonged QRS and QT c intervals and increased T-wave dispersion in dTGRs were reduced by n-3 PUFAs or aliskiren. Both treatments reduced arrhythmia induction from 75% in dTGRs to 17% versus 0% in Sprague-Dawley rats. Macrophage infiltration and fibrosis were reduced by n-3 PUFAs and aliskiren. Connexin 43, a mediator of intermyocyte conduction, was redistributed to the lateral cell membranes in dTGRs. n-3 PUFAs and aliskiren restored normal localization to the intercalated disks. Thus, n-3 PUFAs and aliskiren improved electrical remodeling, arrhythmia induction, and connexin 43 expression, despite a 70-mm Hg difference in blood pressure and the development of cardiac hypertrophy. Key Words: angiotensin II Ⅲ renin inhibition Ⅲ n-3 PUFA Ⅲ arrhythmias Ⅲ magnetocardiography H ypertensive heart disease causes heart failure and arrhythmia propensity. Ischemia, cardiac hypertrophy, fibrosis, inflammation, and electrical remodeling all contribute to the pathogenesis. 1,2 The renin-angiotensin-aldosterone system is a primary driver, and its blockade is state-of-the-art therapy. We provided initial evidence that direct renin inhibition (DRI) in transgenic rats harboring the human renin and angiotensinogen genes (dTGRs) improves target organ damage. 3-5 Untreated dTGRs developed severe hypertension, hypertrophy, inflammation, fibrosis, and small myocardial infarctions. Ventricular arrhythmias and, consequently, sudden cardiac death contributed to the high mortality rate at the early age of 7 weeks. 6 Electrical remodeling in dTGRs included dysregulation of the I to potassium channel, Ca 2ϩ -cycling proteins, and connexin (Cx) 43 gap junctions. 6,7 n-3 polyunsaturated fatty acids (PUFAs), contained in marine fish oil, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lead to cardioprotection and reduce sudden cardiac death. 8 The molecular mechanisms by which n-3 PUFAs exert their cardioprotective effects are not fully understood. n-3 PUFAs putatively affect membran...
Stings in the head region are considered to be a risk factor for severe systemic reactions to hymenoptera stings. We supposed that stings in skin areas, which are well supplied with blood, lead to more severe reactions and tested our hypothesis in 847 patients with confirmed hymenoptera venom allergy. However, symptom severity was independent from sting site: only 16.3% of patients with severe reactions were stung on the head (P = 0.017). But we confirmed age > 40 years (P < 0.001) as well as elevated basal tryptase levels (P = 0.001) as risk factors. Taking antihypertensive drugs seemed to have an influence: 41.7% of patients taking antihypertensive drugs experienced a severe reaction compared to 29.5% of patients, not taking such drugs (P = 0.019). However, considering patients' age in regression analysis, taking antihypertensive drugs had no effect on symptom severity (P = 0.342). Importantly, in most patients with severe reactions, cutaneous signs were absent (P < 0.001).
For many years, only the major allergen rApi m 1 has been available on the ImmunoCAP system for routine diagnosis of bee venom (BV) allergy. Now, there are five components available, and we aimed to detect the sensitivity and specificity of rApi m 1, 2, 3, 5, and 10 in BV-allergic patients. We further evaluated the sensitivity of rApi m 1 and 2 of an alternative platform and investigated possible differences in the sensitization profile between monosensitization and clinically relevant double sensitization. Analysis of the whole panel of BV allergens of the CAP system still resulted in a lower sensitivity than analysis of the combination of rApi m 1 and 2 of the Immulite (71.6% vs 85.8%). Sensitization rate of rApi m 5 was more than doubled in double-sensitized patients, while there was no difference for rApi m 2. The benefit of the commercially available panel of BV components is questionable, due to the insufficient sensitivity and still unavailable important cross-reacting allergens.
Supported by the Austrian Science Fund (FWF) grants SFB F4608 and F4610 and by the Christian Doppler Laboratory for Immunomodulation. Disclosure of potential conflict of interest: C. M€ obs has received research support from the German Research Foundation (DFG), Philipps University Marburg, and the Rh€ on-Klinikum AG and has received travel support from DFG. W. Pf€ utzner has received research support and travel support from DFG, is a member of ALK-Abell o's advisory board on insect venom allergy and house dust mite allergy, has received research support from Philipps University Marburg and the Rh€ on-Klinikum AG, and has received lecture fees from Novartis and ALK-Abell o. B. Bohle has received research support from the Austrian Science Funds and from the Christian Doppler Laboratory for Immunomodulation. The rest of the authors declare that they have no relevant conflicts of interest.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.