Article Impact Level: HIGH Data Quality: STRONG Summary of European Heart Journal, ehad274. https://doi.org/10.1093/eurheartj/ehad274 Dr. Feng Dong et al.
Points
- Takotsubo syndrome (TTS) is linked to coronary microvascular dysfunction (CMD) and abnormalities in myocardial perfusion.
- Vascular Kv1.5 channels, which connect coronary blood flow to myocardial metabolism, play a significant role in CMD.
- A murine model was used to study the association between TTS and CMD by examining wild-type, Kv1.5−/−, and TgKv1.5−/− mice following transaortic constriction (TAC).
- Abnormalities in flow regulation between the left ventricular (LV) apex and base were identified as the cause of TTS, leading to systolic apical ballooning.
- Normalizing myocardial blood flow (MBF) between the LV apex and base brought back ventricular function, and treatment with chromonar reversed some genetic changes that are linked to TTS.
Summary
This research paper uses a murine model to investigate the relationship between Takotsubo syndrome (TTS) and coronary microvascular dysfunction (CMD). The study focuses on the role of vascular Kv1.5 channels in connecting coronary blood flow to myocardial metabolism, and their deletion mimics the CMD phenotype.
To determine the association between TTS and CMD, the researchers studied wild-type (WT), Kv1.5−/−, and TgKv1.5−/− mice following transaortic constriction (TAC). Measurements of left ventricular (LV) fractional shortening (FS) and myocardial blood flow (MBF) were taken using standard and contrast echocardiography. Ribonucleic Acid deep sequencing was performed on LV apex and base samples, and gene expression changes were confirmed by real-time polymerase chain reaction.
The study results revealed that flow regulation abnormalities between the LV apex and base are responsible for TTS. In Kv1.5−/− mice subjected to TAC, systolic apical ballooning was observed, indicated by negative FS. This phenomenon was not observed in WT mice, Kv1.5−/− mice with chromonar (a medication that increases MBF), or TgKv1.5−/− mice. Furthermore, MBF in the LV apex was lower than in the base after TAC in Kv1.5−/− mice. However, increasing MBF with chromonar or in TgKv1.5−/− mice normalized perfusion and function between the LV apex and base. The study also found that some genetic changes associated with TTS were reversed by chromonar, indicating their independence from TAC and their closer relationship to TTS.
In conclusion, this research highlights the crucial role of flow regulation abnormalities between the LV apex and base in developing TTS. Normal ventricular function is restored when perfusion is normalized between these two regions. The findings suggest a connection between CMD and TTS, with the deletion of vascular Kv1.5 channels mimicking the CMD phenotype. This study provides valuable insights into the underlying mechanisms of TTS and contributes to a better understanding of this puzzling syndrome.
Link to the article: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehad274/7160508
References Dong, F., Yin, L., Sisakian, H., Hakobyan, T., Jeong, L. S., Joshi, H., Hoff, E., Chandler, S., Srivastava, G., Jabir, A. R., Kimball, K., Chen, Y.-R., Chen, C.-L., Kang, P. T., Shabani, P., Shockling, L., Pucci, T., Kegecik, K., Kolz, C., … Ohanyan, V. (2023). Takotsubo syndrome is a coronary microvascular disease: Experimental evidence. European Heart Journal, ehad274. https://doi.org/10.1093/eurheartj/ehad274
