Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.4.3.13 (
lysyl oxidase
)
1,248
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Secreted
phospholipase A
2
-IIA (sPLA
2
-IIA) is a pro-inflammatory protein associated with cardiovascular disorders, whose functions and underlying mechanisms in cardiac remodelling are still under investigation. We herein study the role of sPLA
2
-IIA in cardiac fibroblast (CFs)-to-myofibroblast differentiation and fibrosis, two major features involved in cardiac remodelling, and also explore potential mechanisms involved. In a mice model of dilated cardiomyopathy (DCM) after autoimmune myocarditis, serum and cardiac sPLA
2
-IIA protein expression were found to be increased, together with elevated cardiac levels of the cross-linking enzyme
lysyl oxidase
(
LOX
) and reactive oxygen species (ROS) accumulation. Exogenous sPLA
2
-IIA treatment induced proliferation and differentiation of adult rat CFs. Molecular studies demonstrated that sPLA
2
-IIA promoted Src phosphorylation, shedding of the membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) ectodomain and EGFR phosphorylation, which triggered phosphorylation of ERK, P70S6K and rS6. This was also accompanied by an up-regulated expression of the bone morphogenic protein (BMP)-1,
LOX
and collagen I. ROS accumulation were also found to be increased in sPLA
2
-IIA-treated CFs. The presence of inhibitors of the Src/ADAMs-dependent HB-EGF shedding/EGFR pathway abolished the CF phenotype induced by sPLA
2
-IIA. In conclusion, sPLA
2
-IIA may promote myofibroblast differentiation through its ability to modulate EGFR transactivation and signalling as key mechanisms that underlie its biological and pro-fibrotic effects.
...
PMID:Secreted Phospholipase A
2
-IIA Modulates Transdifferentiation of Cardiac Fibroblast through EGFR Transactivation: An Inflammation-Fibrosis Link. 3204 47
Aortic dissection is a life-threatening aortopathy involving separation of the aortic wall, whose underlying mechanisms are still incompletely understood. Epidemiological evidence suggests that unsaturated fatty acids improve cardiovascular health. Here, using quantitative RT-PCR, histological analyses, magnetic cell sorting and flow cytometry assays, and MS-based lipidomics, we show that the activity of a lipid-metabolizing enzyme, secreted
phospholipase A
2
group V (sPLA
2
-V), protects against aortic dissection by endogenously mobilizing vasoprotective lipids. Global and endothelial cell-specific sPLA
2
-V-deficient mice frequently developed aortic dissection shortly after infusion of angiotensin II (AT-II). We observed that in the AT-II-treated aorta, endothelial sPLA
2
-V mobilized oleic and linoleic acids, which attenuated endoplasmic reticulum stress, increased the expression of
lysyl oxidase
, and thereby stabilized the extracellular matrix in the aorta. Of note, dietary supplementation with oleic or linoleic acid reversed the increased susceptibility of sPLA
2
-V-deficient mice to aortic dissection. These findings reveal an unexplored functional link between sPLA
2
-driven phospholipid metabolism and aortic stability, possibly contributing to the development of improved diagnostic and/or therapeutic strategies for preventing aortic dissection.
...
PMID:Group V secreted phospholipase A
2
plays a protective role against aortic dissection. 3248 92
