Altering Calcium Sensitivity in Heart Failure: A Crossroads of Disease Etiology and Therapeutic Innovation.
Int J Mol Sci
; 24(24)2023 Dec 17.
Article
em En
| MEDLINE
| ID: mdl-38139404
ABSTRACT
Heart failure (HF) presents a significant clinical challenge, with current treatments mainly easing symptoms without stopping disease progression. The targeting of calcium (Ca2+) regulation is emerging as a key area for innovative HF treatments that could significantly alter disease outcomes and enhance cardiac function. In this review, we aim to explore the implications of altered Ca2+ sensitivity, a key determinant of cardiac muscle force, in HF, including its roles during systole and diastole and its association with different HF types-HF with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). We further highlight the role of the two rate constants kon (Ca2+ binding to Troponin C) and koff (its dissociation) to fully comprehend how changes in Ca2+ sensitivity impact heart function. Additionally, we examine how increased Ca2+ sensitivity, while boosting systolic function, also presents diastolic risks, potentially leading to arrhythmias and sudden cardiac death. This suggests that strategies aimed at moderating myofilament Ca2+ sensitivity could revolutionize anti-arrhythmic approaches, reshaping the HF treatment landscape. In conclusion, we emphasize the need for precision in therapeutic approaches targeting Ca2+ sensitivity and call for comprehensive research into the complex interactions between Ca2+ regulation, myofilament sensitivity, and their clinical manifestations in HF.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Disfunção Ventricular Esquerda
/
Insuficiência Cardíaca
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article