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Activation of the Aryl Hydrocarbon Receptor in Muscle Exacerbates Ischemic Pathology in Chronic Kidney Disease
CONCLUSIONS: These findings establish AHR activation in muscle as a pivotal regulator of the ischemic limb pathology in CKD. Further, the totality of the results provides support for testing of clinical interventions that diminish AHR signaling in these conditions.PMID:37325935 | DOI:10.1161/CIRCRESAHA.123.322875
Source: Circulation Research - June 16, 2023 Category: Cardiology Authors: Nicholas Balestrieri Victoria Palzkill Caroline Pass Jianna Tan Zachary R Salyers Chatick Moparthy Ania Murillo Kyoungrae Kim Trace Thome Qingping Yang Kerri A O'Malley Scott A Berceli Feng Yue Salvatore T Scali Leonardo F Ferreira Terence E Ryan Source Type: research

Chronic activation of the aryl hydrocarbon receptor in muscle exacerbates ischemic pathology in chronic kidney disease
bioRxiv. 2023 May 18:2023.05.16.541060. doi: 10.1101/2023.05.16.541060. Preprint.ABSTRACTChronic kidney disease (CKD) accelerates the development of atherosclerosis, decreases muscle function, and increases the risk of amputation or death in patients with peripheral artery disease (PAD). However, the cellular and physiological mechanisms underlying this pathobiology are ill-defined. Recent work has indicated that tryptophan-derived uremic toxins, many of which are ligands for the aryl hydrocarbon receptor (AHR), are associated with adverse limb outcomes in PAD. We hypothesized that chronic AHR activation, driven by the acc...
Source: Atherosclerosis - June 9, 2023 Category: Cardiology Authors: Nicholas Balestrieri Victoria Palzkill Caroline Pass Jianna Tan Zachary R Salyers Chatick Moparthy Ania Murillo Kyoungrae Kim Trace Thome Qingping Yang Kerri A O'Malley Scott A Berceli Feng Yue Salvatore T Scali Leonardo F Ferreira Terence E Ryan Source Type: research

A Swine Hind Limb Ischemia Model Useful for Testing Peripheral Artery Disease Therapeutics
AbstractCurrently, there is no large animal model of sustained limb ischemia suitable for testing novel angiogenic therapeutics for peripheral artery disease (PAD) such as drugs, genes, materials, or cells. We created a large animal model suitable for efficacy assessment of these therapies by testing 3 swine hind limb ischemia (HLI) variations and quantifying vascular perfusion, muscle histology, and limb function. Ligation of the ipsilateral external and bilateral internal iliac arteries produced sustained gait dysfunction compared to isolated external iliac or unilateral external and internal iliac artery ligations. Hype...
Source: Journal of Cardiovascular Translational Research - December 1, 2021 Category: Cardiology Source Type: research

Mechanism of Hydrogen Sulfide Preconditioning-Associated Protection Against Ischemia-Reperfusion Injury Differs in Diabetic Heart That Develops Myopathy.
Abstract Hydrogen sulfide (H2S) is reported to be effective in the management of the myocardial ischemia-reperfusion (I/R) injury via PI3K/GSK3β pathway in normal rats. However, its efficacy against I/R in the presence of diabetic cardiomyopathy is relatively obscure. Thus, the present work aimed to find out H2S-mediated cardioprotection against I/R in diabetic cardiomyopathy and to evaluate its mode of action using Langendorff isolated heart perfusion system. The present work includes three groups of rat, viz. (i) normal, (ii) diabetes mellitus (DM: streptozotocin: 35 mg/kg; normal diet), and (iii) diabetes +...
Source: Cardiovascular Toxicology - July 16, 2019 Category: Cardiology Authors: Ansari M, Kurian GA Tags: Cardiovasc Toxicol Source Type: research

A BAG3 Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.
Conclusions -Taken together, our data demonstrate that genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis. These results highlight a pathway that preserves tissue survival and muscle function in the setting of ischemia. PMID: 28442482 [PubMed - as supplied by publisher]
Source: Circulation - April 25, 2017 Category: Cardiology Authors: McClung JM, McCord TJ, Ryan TE, Schmidt CA, Green TD, Southerland KW, Reinardy JL, Mueller SB, Venkatraman TN, Lascola CD, Keum S, Marchuk DA, Spangenburg EE, Dokun AO, Annex BH, Kontos CD Tags: Circulation Source Type: research