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:2.7.11.17 (
CaMKII
)
4,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In patients with diabetes, impaired activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), the plasma metalloprotease that cleaves highly thrombogenic von Willebrand factor multimers, is a major risk factor of cardiovascular events. Here, using
Adamts13
-/-
mice made diabetic by streptozotocin, we investigated the impact of the lack of ADAMTS13 on the development of diabetes-associated end-organ complications.
Adamts13
-/-
mice experienced a shorter life span than their diabetic wild-type littermates. It was surprising that animal death was not related to the occurrence of detectable thrombotic events. The lack of ADAMTS13 drastically increased the propensity for ventricular arrhythmias during dobutamine-induced stress in diabetic mice. Cardiomyocytes of diabetic
Adamts13
-/-
mice exhibited an aberrant distribution of the ventricular gap junction connexin 43 and increased phosphorylation of Ca
2+
/
calmodulin-dependent kinase II
(
CaMKII
), and with the consequent
CaMKII
-induced disturbance in Ca
2+
handling, which underlie propensity for arrhythmia. In vitro,
thrombospondin 1
(
TSP1
) promoted, in a paracrine manner,
CaMKII
phosphorylation in murine HL-1 cardiomyocytes, and ADAMTS13 acted to inhibit
TSP1
-induced
CaMKII
activation. In conclusion, the deficiency of ADAMTS13 may underlie the onset of lethal arrhythmias in diabetes through increased
CaMKII
phosphorylation in cardiomyocytes. Our findings disclose a novel function for ADAMTS13 beyond its antithrombotic activity.
...
PMID:ADAMTS13 Deficiency Shortens the Life Span of Mice With Experimental Diabetes. 2997 18
