2024年1月2日 · Mice heterozygous for Pkd2 have attenuated NP responses and we hypothesized that cardiomyocyte-localized polycystin proteins contribute to production of NPs. Cardiomyocyte-specific knock-out models of polycystin-2 (PC2), one of the causative genes of ADPKD, demonstrate diurnal hypertension.

2008年2月1日 · This review provides a primer on PKD signaling, using information gained from studies in multiple cell types, and discusses recent data that suggest novel functions for PKD-mediated pathways in the heart and the circulation.

In zebrafish, early blood flow in the heart generates mechanical signals that are transduced by Pkd2 in atrioventricular endocardial cells. This regulates intracellular calcium ion concentration, activating Camk2g, which promotes Klf2a expression and valve formation.

Pkd2 mutant zebrafish display reduced cardiac output, atrioventricular block, and edema. Pkd2 mutant hearts show prolonged Ca 2+ transients and Ca 2+ alternans. Pacing increases resting Ca 2+ levels and decreases Ca 2+ cycling in pkd2 mutant hearts. ADPKD is associated with an increased prevalence of IDCM

Our current research focused mainly on the impact of Pkd2 gene mutation on heart tissues and functions. Based on the structural changes in the heart tissues, we showed clear evidence of cardiac remodeling, including LV hypertrophy, and interstitial fibrosis.

我们发现巨噬细胞 1 (M1) 和巨噬细胞 2 (M2) 浸润、转化生长因子 (TGF-b 1 ) 和 TGF-b 1 受体表达在 PKd2 -KO，与野生型心脏相比。 细胞外基质增加 PKd2 -KO心肌导致心脏肥大、间质和传导系统纤维化，导致心功能不全并易发生心律失常。 左心室 (LV) 扩张或顺应性和 LV 充盈在纤维化中受损 PKd2 -KO 心脏，导致舒张功能障碍。 LV 收缩性和弹性在纤维化中降低 PKd2 -KO 心脏，导致收缩功能障碍。 与野生型心脏相比， PKd2 -KO 心脏对药理压力测试和前负荷变化的反应 …

Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. In human ADPKD patients, we found IDCM to coexist frequently with ADPKD. This association was strongest in patients with PKD2 mutations.

Although autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple kidney cysts, the most frequent cause of death in ADPKD patients is cardiovascular disease. ADPKD is linked to mutations in pkd1 or pkd2, the genes that encode for the proteins polycystin 1 and polycystin 2 (PC1 and PC2, respectively ...

Although stimulus-specific activation patterns for PKD1, PKD2, and PKD3 have been identified in cardiomyocytes, progress toward identifying PKD isoform-specific functions in the heart have been hampered by significant gaps in our understanding of the molecular mechanisms that regulate PKD activity.

2016年4月15日 · Mutations in the gene for polycystin 2 (Pkd2) lead to polycystic kidney disease, however the main cause of mortality in humans is cardiac related. We previously showed that 5 month old Pkd2+/- mice have altered calcium-contractile activity in cardiomyocytes, but have preserved cardiac function.