کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6161160 | 1249364 | 2016 | 18 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1cond/condNestincre (CYG+) cystic mice exposed to increased blood pressure, at 5 to 6 and 20 to 24 weeks of age, and Pkd1+/- (HTG+) noncystic mice at 5-6 and 10-13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1cond/cond and Pkd1+/+ controls. Hearts from CYG+Â and HTG+ mice presented reduced polycystin-1 expression, increased apoptosis, and mild fibrosis. Since galectin-3 has been associated with heart dysfunction, we studied it as a potential modifier of the ADPKD cardiac phenotype. Double-mutant Pkd1cond/cond:Nestincre;Lgals3-/- (CYG-) and Pkd1+/-;Lgals3-/- (HTG-) mice displayed improved cardiac deformability and systolic parameters compared to single-mutants, not differing from the controls. CYG- and HTG- showed decreased apoptosis and fibrosis. Analysis of a severe cystic model (Pkd1V/V; VVG+) showed that Pkd1V/V;Lgals3-/- (VVG-) mice have longer survival, decreased cardiac apoptosis and improved heart function compared to VVG+. CYG- and VVG- animals showed no difference in renal cystic burden compared to CYG+ and VVG+ mice. Thus, myocardial dysfunction occurs in different Pkd1-deficient models and suppression of galectin-3 expression rescues this phenotype.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 90, Issue 3, September 2016, Pages 580-597
Journal: Kidney International - Volume 90, Issue 3, September 2016, Pages 580-597
نویسندگان
Bruno E. Balbo, Andressa G. Amaral, Jonathan M. Fonseca, Isac de Castro, Vera M. Salemi, Leandro E. Souza, Fernando dos Santos, Maria C. Irigoyen, Feng Qian, Roger Chammas, Luiz F. Onuchic,