Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assessed the role of nitric oxide (NO) and the kinin B2 receptor in mediating tissue kallikrein's actions in intramyocardial inflammation and cardiac remodeling after ischemia/reperfusion (I/R) injury. Adenovirus carrying the human tissue kallikrein gene was delivered locally into rat hearts 4 days prior to 30-minute ischemia followed by 24-hour or 7-day reperfusion with or without administration of icatibant, a kinin B2 receptor antagonist, or N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. Kallikrein gene delivery improved cardiac contractility and diastolic function, reduced infarct size at 1 day after I/R without affecting mean arterial pressure. Kallikrein treatment reduced macrophage/monocyte and neutrophil accumulation in the infarcted myocardium in association with reduced intercellular adhesion molecule-1 levels. Kallikrein increased cardiac endothelial nitric oxide synthase phosphorylation and NO levels and decreased superoxide formation, TGF-beta1 levels and Smad2 phosphorylation. Furthermore, kallikrein reduced I/R-induced JNK, p38MAPK, IkappaB-alpha phosphorylation and nuclear NF-kappaB activation. In addition, kallikrein improved cardiac performance, reduced infarct size and prevented ventricular wall thinning at 7 days after I/R. The effects of kallikrein on cardiac function, inflammation and signaling mediators were all blocked by icatibant and L-NAME. These results indicate that tissue kallikrein through kinin B2 receptor and NO formation improves cardiac function, prevents inflammation and limits left ventricular remodeling after myocardial I/R by suppression of oxidative stress, TGF-beta1/Smad2 and JNK/p38MAPK signaling pathways and NF-kappaB activation.
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PMID:Nitric oxide mediates cardiac protection of tissue kallikrein by reducing inflammation and ventricular remodeling after myocardial ischemia/reperfusion. 1806 96

The incidence of cardiovascular thrombotic events which are highly associated with atherosclerotic plaque vulnerability and its rupture is much higher in chronic kidney disease (CKD) patients than that in the general population. It has been reported that the thinning of fibrous cap in atherosclerotic plaque is a crucial factor in plaque vulnerability and thrombosis. Moreover, vascular smooth muscle cells (VSMCs) senescence play a crucial role in maintaining the thickness of fibrous cap. Lamin B1, one of the members of laminin family, is an important component of the nuclear membrane and it is related to cell senescence. While whether lamin B1 participates CKD-related VSMCs senescence and plaque vulnerability and the underlying mechanism remain unclear. Here, we found that CKD promoted fibrous cap thinning and reduced the stability of atherosclerotic plaque through accelerating VSMCs senescence. VSMCs senescence induced by CKD was related to the increased expression of lamin B1 and abnormality of nuclear membrane structure. Knocking down the expression of lamin B1 with RNA interference prevented CKD-induced aberrant nuclear membrane structure and senescence in VSMCs. Additionally, overproduction of reactive oxidative stress (ROS) and subsequent activation of ROS/p38MAPK under CKD milieus contribute to these series of outcomes, as scavenging ROS with N-acety-l-cysteine (NAC) or inhibiting p38MAPK signal pathway with SB203580 could inhibit CKD-induced activation of ROS/p38MAPK, increased expression of lamin B1, abnormality of nuclear membrane structure and VSMCs senescence. Taken together, these results suggested that ROS/p38MAPK-mediated increased expression of lamin B1 and abnormality of nuclear membrane structure was an important mechanism of CKD-induced VSMCs senescence.
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PMID:ROS/p38MAPK-induced lamin B1 accumulation promotes chronic kidney disease-associated vascular smooth muscle cells senescence. 3278 68