Key result
GCaMP2 transgenic rats exhibited a marked deterioration of left ventricular active relaxation compared to controls (τ: 16.8 vs 12.2 ms, P<0.001), along with cardiac hypertrophy and hypertension.
Why the study?
To investigate whether expression of the genetically engineered calcium sensor protein GCaMP2 itself affects cardiac function.
Absolute Event Rate: 16.8% vs 12.2%
p-value: p=<0.001
The GCaMP2 transgenic rat model exhibits baseline cardiac hypertrophy, arterial hypertension, and impaired LV relaxation, indicating that caution is needed when using this model for cardiovascular studies.
Baseline cardiac abnormalities in GCaMP2 rats warrant caution in cardiovascular research use; leaves open their validity as neutral controls.
A novel transgenic rat strain has recently been generated that stably expresses the genetically engineered calcium sensor protein GCaMP2 in different cell types, including cardiomyocytes, to investigate calcium homeostasis. To investigate whether the expression of the GCaMP2 protein itself affects cardiac function, in the present work we aimed at characterizing in vivo hemodynamics in the GCaMP2 transgenic rat strain. GCaMP2 transgenic rats and age-matched Sprague-Dawley control animals were investigated. In vivo hemodynamic characterization was performed by left ventricular (LV) pressure-volume analysis. Postmortem heart weight data showed cardiac hypertrophy in the GCaMP2 group (heart-weight-to-tibial-length ratio: 0.26 ± 0.01 GCaMP2 vs. 0.23 ± 0.01 g/cm Co, P < 0.05). We detected elevated mean arterial pressure and increased total peripheral resistance in transgenic rats. GCaMP2 transgenesis was associated with prolonged contraction and relaxation. LV systolic function was not altered in transgenic rats, as indicated by conventional parameters and load-independent, sensitive indices. We found a marked deterioration of LV active relaxation in GCaMP2 animals (τ: 16.8 ± 0.7 GCaMP2 vs. 12.2 ± 0.3 ms Co, P < 0.001). Our data indicated myocardial hypertrophy, arterial hypertension, and impaired LV active relaxation along with unchanged systolic performance in the heart of transgenic rats expressing the GCaMP2 fluorescent calcium sensor protein. Special caution should be taken when using transgenic models in cardiovascular studies. NEW & NOTEWORTHY Genetically encoded Ca 2+ -sensors, like GCaMP2, are important tools to reveal molecular mechanisms for Ca 2+ -sensing. We provided left ventricular hemodynamic characterization of GCaMP2 transgenic rats and found increased afterload, cardiac hypertrophy, and prolonged left ventricular relaxation, along with unaltered systolic function and contractility. Special caution should be taken when using this rodent model in cardiovascular pharmacological and toxicological studies.
No takes yet. Share an insight, caveat, or question.
Oláh et al. (2019) studied this question. GCaMP2 transgenesis vs. Age-matched Sprague-Dawley control animals was evaluated on Left ventricular active relaxation (τ) (p=<0.001). GCaMP2 transgenic rats exhibited a marked deterioration of left ventricular active relaxation compared to controls (τ: 16.8 vs 12.2 ms, P<0.001), along with cardiac hypertrophy and hypertension.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: