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Fine-tuning of microglia polarization prevents diabetes-associated cerebral atherosclerosis
In this study, we showed that polarization of microglia, the resident macrophage in the central nervous system, appeared to play a critical role in the pathological progression of cerebral atherosclerosis. Microglia likely underwent an M2c-like polarization in an environment long exposed to high glucose. Experimental suppression of microglia M2c polarization was achieved through transduction of microglia with an adeno-associated virus (serotype AAV-PHP.B) carrying siRNA for interleukin-10 (IL-10) under the control of a microglia-specific TMEM119 promoter, which significantly attenuated diabetes-associated cerebral atherosc...
Source: Atherosclerosis - August 8, 2022 Category: Cardiology Authors: Xuan Zhu Pengfei Xing Ping Zhang Minmin Zhang Hongjian Shen Lei Chen Fang Shen Yi Jiang Hui Yuan Lei Zhang Jing Wang Xiongfeng Wu Yu Zhou Tao Wu Benqiang Deng Jianmin Liu Yongwei Zhang Pengfei Yang Source Type: research

Lipid Lowering Therapy: An Era Beyond Statins
Curr Probl Cardiol. 2022 Jul 30:101342. doi: 10.1016/j.cpcardiol.2022.101342. Online ahead of print.ABSTRACTDyslipidemia, specifically elevated LDL cholesterol levels, causes atherosclerotic cardiovascular disease (ASCVD) and increases the risk of myocardial infarction and stroke. Statins, a class of drugs that exert their effects by inhibiting HMG-CoA reductase, a key enzyme in the synthesis of cholesterol, have been the mainstay of therapy for the primary prevention of cardiovascular disease and lipids reduction. Statins are associated with side effects, most commonly myopathy and myalgias, despite their proven efficacy....
Source: Atherosclerosis - August 2, 2022 Category: Cardiology Authors: Toufik Abdul-Rahman Syed Muhammad Awais Bukhari Emiliano Cantu Herrera Wireko Andrew Awuah Jannel Lawrence Heloisa de Andrade Neal Patel Rohan Shah Raheel Shaikh Camilo Andr és Avendaño Capriles Sebahat Ulusan Shahzaib Ahmad Anna Corriero Adriana C Mare Source Type: research

Po-626-03 preclinical safety of adkcnh2-g628s for post-op af
Post-operative atrial fibrillation (POAF) occurs in 30% of cardiac surgeries, increasing risk of stroke, MI, and death. We propose gene therapy with an adenovirus encoding the G628S mutation of KCNH2 (AdKCNH2-G628S) to prevent POAF. We have reported preclinical efficacy in pigs.
Source: Heart Rhythm - April 29, 2022 Category: Cardiology Authors: J. Kevin Donahue, David D. McManus Source Type: research

Ablation of Plasma Prekallikrein Decreases LDL Cholesterol by Stabilizing LDL Receptor and Protects against Atherosclerosis
Conclusions: PK regulates circulating cholesterol levels through binding to LDLR and inducing its lysosomal degradation. Ablation of PK stabilizes LDLR, decreases LDL cholesterol and prevents atherosclerotic plaque development. This study suggests that PK is a promising therapeutic target to treat ASCVD.PMID:35189703 | DOI:10.1161/CIRCULATIONAHA.121.056491
Source: Atherosclerosis - February 22, 2022 Category: Cardiology Authors: Jin-Kai Wang Yang Li Xiao-Lu Zhao Yuan-Bin Liu Jing Tan Yu-Ying Xing Dilare Adi Yong-Tao Wang Zhen-Yan Fu Yi-Tong Ma Song-Mei Liu Yong Liu Yan Wang Xiong-Jie Shi Xiao-Yi Lu Bao-Liang Song Jie Luo Source Type: research

KLF11 (Kru üppel-Like Factor 11) Inhibits Arterial Thrombosis via Suppression of Tissue Factor in the Vascular Wall.
Conclusions- Our data demonstrate that KLF11 is a novel transcriptional suppressor of F3 in vascular smooth muscle cells, constituting a potential molecular target for inhibition of arterial thrombosis. PMID: 30602303 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - January 3, 2019 Category: Cardiology Authors: Liang W, Fan Y, Lu H, Chang Z, Hu W, Sun J, Wang H, Zhu T, Wang J, Adili R, Garcia-Barrio MT, Holinstat M, Eitzman D, Zhang J, Chen YE Tags: Arterioscler Thromb Vasc Biol Source Type: research

Experimental cardiac radiation exposure induces ventricular diastolic dysfunction with preserved ejection fraction
Breast cancer radiotherapy increases the risk of heart failure with preserved ejection fraction (HFpEF). Cardiomyocytes are highly radioresistant, but radiation specifically affects coronary microvascular endothelial cells, with subsequent microvascular inflammation and rarefaction. The effects of radiation on left ventricular (LV) diastolic function are poorly characterized. We hypothesized that cardiac radiation exposure may result in diastolic dysfunction without reduced EF. Global cardiac expression of the sodium-iodide symporter (NIS) was induced by cardiotropic gene (adeno-associated virus serotype 9) delivery to 5-w...
Source: AJP: Heart and Circulatory Physiology - August 11, 2017 Category: Cardiology Authors: Saiki, H., Moulay, G., Guenzel, A. J., Liu, W., Decklever, T. D., Classic, K. L., Pham, L., Chen, H. H., Burnett, J. C., Russell, S. J., Redfield, M. M. Tags: RESEARCH ARTICLE 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

Neuron-Specific Tumor Necrosis Factor Receptor-Associated Factor 3 Is a Central Regulator of Neuronal Death in Acute Ischemic Stroke Nervous System
Neuronal death after ischemic stroke involves multiple pathophysiological events, as well as a complex molecular mechanism. Inhibiting a single therapeutic target that is involved in several ischemic signaling cascades may be a promising strategy for stroke management. Here, we report the versatile biological roles of tumor necrosis factor receptor–associated factor 3 (TRAF3) in ischemic stroke. Using several genetically manipulated mouse strains, we also demonstrated that TRAF3 inhibition can be neuroprotective. TRAF3 expression, which is robustly induced in response to ischemia/reperfusion (I/R) injury, was detecte...
Source: Hypertension - August 12, 2015 Category: Cardiology Authors: Gong, J., Li, Z.-Z., Guo, S., Zhang, X.-J., Zhang, P., Zhao, G.-N., Gao, L., Zhang, Y., Zheng, A., Zhang, X.-F., Xiang, M., Li, H. Tags: Apoptosis, Ischemic biology - basic studies, Acute Cerebral Infarction, Oxidant stress Nervous System Source Type: research

SOD1 overexpression prevents acute hyperglycemia-induced cerebral myogenic dysfunction: relevance to contralateral hemisphere and stroke outcomes
In conclusion, our results show that SOD1 overexpression nullified the detrimental effects of HG on myogenic tone and stroke outcomes and that the contralateral hemisphere may be a novel target for the management of acute hyperglycemic stroke.
Source: AJP: Heart and Circulatory Physiology - March 1, 2015 Category: Cardiology Authors: Coucha, M., Li, W., Hafez, S., Abdelsaid, M., Johnson, M. H., Fagan, S. C., Ergul, A. Tags: INTEGRATIVE CARDIOVASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY Source Type: research

Stem Cell Factor Gene Transfer Improves Cardiac Function After Myocardial Infarction in Swine Original Articles
Conclusions— Local overexpression of SCF post-MI induces the recruitment of c-kit+ cells at the infarct border area acutely. In the chronic stages, SCF gene transfer was associated with improved cardiac function in a preclinical model of ischemic cardiomyopathy.
Source: Circulation: Heart Failure - January 20, 2015 Category: Cardiology Authors: Ishikawa, K., Fish, K., Aguero, J., Yaniz-Galende, E., Jeong, D., Kho, C., Tilemann, L., Fish, L., Liang, L., Eltoukhy, A. A., Anderson, D. G., Zsebo, K., Costa, K. D., Hajjar, R. J. Tags: Angiogenesis, Myogenesis, Other Treatment, Acute myocardial infarction Original Articles Source Type: research