Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress caused by an imbalance in the formation and removal of reactive oxygen species (ROS) plays an important role in the development of several cardiovascular diseases. ROS originate from various cellular origins; however, the highest amount of ROS is produced by mitochondria. One of the proteins contributing to mitochondrial ROS formation is the adaptor protein p66shc, which upon cellular stresses translocates from the cytosol to the mitochondria. In the present review, we focus on the role of p66shc in longevity, in the development of cardiovascular diseases including diabetes, atherosclerosis and its risk factors, myocardial ischemia/reperfusion injury and the protection from it by ischemic preconditioning. Also, the contribution of p66shc towards cerebral pathologies and the potential of the protein as a therapeutic target for the treatment of the aforementioned diseases are discussed.
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PMID:P66shc and its role in ischemic cardiovascular diseases. 3116 72

Inflammation, especially involving the NLRP3 inflammasome, is critical to atherosclerotic plaque formation. Enhanced autophagy can inhibit the development of atherosclerosis, and recent studies have revealed that NLRP3 inflammasome can be degraded by autophagy in atherosclerosis. In the present study, we established a foam-cell model to investigate the impact of oxidized low density lipoproteins (ox-LDLs) on autophagy and the inflammasome in atherosclerosis-related inflammation. We observed that ox-LDLs activated NLRP3 inflammasomes in macrophages and restricted autophagy in a time-and dose-dependent manner. We further observed through immunoprecipitation and siRNA knockdown that autophagic degradation of the NLRP3 inflammasome is dependent on K63 polyubiquitation of its NLRP3 subunit and subsequent binding by the adaptor protein p62. Our findings uncover a mechanism by which autophagy inhibits inflammation in atherosclerosis and the role of K63 in that process.
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PMID:K63 ubiquitin chains target NLRP3 inflammasome for autophagic degradation in ox-LDL-stimulated THP-1 macrophages. 3200 54

p62/SQSTM1, encoded by gene SQSTM1, is widely known as an adaptor protein of selective autophagy to promote aggregate-prone proteins for degradation. It is also a stress-induced scaffold protein involved in Nrf2 activation to resist oxidative stress. Multiple domains of p62 interact with several essential pathways implicated in cell differentiation and proliferation, placing p62 at a significant position to mediate cell survival and apoptosis. The p62 protein has been suggested as a potential target in recent years, since its abnormal expression or SQSTM1 gene mutation is tightly associated with various diseases including cancer such as hepatocellular carcinoma and prostate cancer, neurodegenerative disorders such as Alzheimer's disease and amyotrophic lateral sclerosis, atherosclerosis, and Paget's disease of bone. In this review, we will discuss the relationship between p62 and these diseases, and we attempt to put forward novel methods for current diagnosis or therapy by regulating the p62 expression level.
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PMID:p62/SQSTM1, a Central but Unexploited Target: Advances in Its Physiological/Pathogenic Functions and Small Molecular Modulators. 3232 96

Caspase recruitment domain containing protein 9 (CARD9) is an adaptor protein that plays a critical role in pattern recognition receptors (PRRs)-mediated activation of NF-?B and mitogen-activated protein kinase (MAPK). This elicits initiation of the pro-inflammatory cytokines and leads to inflammatory responses, which has been recognized as a critical contributor to chronic inflammation. Current researches demonstrate that CARD9 is strongly associated with metabolic diseases, such as obesity, insulin resistance, atherosclerosis and so on. In this review, we summarize CARD9 signaling pathway and the role of CARD9 in metabolic diseases.
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PMID:The Role of CARD9 in Metabolic Diseases. 3268 Dec 66


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