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)
Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in
dilated cardiomyopathy
. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and
lysyl oxidase
(
LOX
) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and
LOX
activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart.
...
PMID:Role of copper and homocysteine in pressure overload heart failure. 1867 30
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
