Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout

Area of Science:

• Cardiovascular Research
• Nephrology
• Genetics

Background:

• Autosomal dominant polycystic kidney disease (ADPKD) is linked to cardiovascular issues, including myocardial texture alterations.
• The exact mechanisms driving cardiac dysfunction in ADPKD, particularly concerning polycystin-1 deficiency, require further elucidation.

Purpose of the Study:

• To investigate the pathogenesis of cardiac dysfunction in ADPKD models.
• To assess the role of galectin-3 as a potential modifier of the ADPKD cardiac phenotype.

Main Methods:

• Echocardiography was used to analyze cardiac function in Pkd1-deficient mouse models (CYG+ and HTG+) under varying conditions.
• Expression of polycystin-1, apoptosis, fibrosis, and galectin-3 levels were examined in cardiac tissues.
• Studies involved genetically modified mice with targeted deletion of galectin-3 (Lgals3(-/-)) to evaluate its impact on cardiac phenotype and survival.

Main Results:

• Pkd1-deficient mice (CYG+ and HTG+) exhibited impaired myocardial deformation, systolic dysfunction, and diastolic dysfunction.
• Reduced polycystin-1 expression, increased cardiac apoptosis, and mild fibrosis were observed in affected mice.
• Suppression of galectin-3 in double-mutant mice (CYG- and HTG-) significantly improved cardiac function, reduced apoptosis and fibrosis, and enhanced survival in a severe cystic model (VVG-).
• Galectin-3 suppression did not affect renal cystic burden.

Conclusions:

• Myocardial dysfunction is a significant manifestation in various Pkd1-deficient models.
• Galectin-3 plays a crucial role in mediating cardiac dysfunction in ADPKD.
• Targeting galectin-3 represents a potential therapeutic strategy to ameliorate cardiac complications in ADPKD.