2026/03/01 by André M. Leite‐Moreira, João Almeida‐Coelho, Inês Falcão‐Pires +2 · 1 voice
Medicine · #Cardiac Fibrosis and Remodeling #Cardiomyopathy and Myosin Studies #Cardiovascular Function and Risk Factors
paper · doi:10.14814/phy2.70709
openalex publication_date 2026/03/01 · openalex created_date 2026/03/20 · openalex updated_date 2026/07/31
Abstract The heart constantly adapts to acute hemodynamic load by increasing contractility and stretch‐induced compliance (SIC). The latter involves titin phosphorylation, notably by cGMP‐dependent protein kinase (PKG). Given that Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII) also phosphorylates titin and is activated under acute stress via redox signaling, we hypothesized a role for CaMKII in SIC. We assessed passive tension (PT) decay in the 15 min following sudden stretch in isometrically contracting rabbit right ventricular papillary muscles, with or without PKG or CaMKII inhibition. Additionally, Wistar Han rat hearts were Langendorff‐perfused and acutely stretched or left unstretched. Skinned cardiomyocytes extracted from these hearts were analyzed for sarcomere length‐PT relationships before and after incubation with PKG, CaMKII, or both. Both kinases reduced PT, with diminished effects in pre‐stretched cells, suggesting prior kinase activation. PKG inhibition significantly blunted SIC, while CaMKII inhibition showed a similar but non‐significant trend. Our findings support that CaMKII contributes to SIC, likely via shared phosphorylation targets with PKG. These results provide mechanistic insight into SIC and suggest CaMKII as a potential modulator of diastolic function during acute stretch, such as in preload challenges.