β1-Adrenergic receptors stimulate cardiac contractility and CaMKII activation in vivo and enhance cardiac dysfunction following myocardial infarction
Autor: | Antonio Curcio, Lan Mao, Howard A. Rockman, Byung Su Yoo, Anthony Lemaire, Supachoke Mangmool, Matthew J. Wolf |
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Jazyk: | angličtina |
Rok vydání: | 2009 |
Předmět: |
Cardiac function curve
medicine.medical_specialty Time Factors Adrenergic receptor Physiology Myocardial Infarction Stimulation Apoptosis Contractility Mice Ventricular Dysfunction Left Heart Rate Physiology (medical) Ca2+/calmodulin-dependent protein kinase Internal medicine medicine Ventricular Pressure Animals Receptor Mice Knockout business.industry Myocardium Isoproterenol Stroke Volume Articles Adrenergic beta-Agonists medicine.disease Myocardial Contraction Enzyme Activation Mice Inbred C57BL Disease Models Animal Endocrinology Adrenergic beta-1 Receptor Agonists Heart failure cardiovascular system Receptors Adrenergic beta-2 Signal transduction Receptors Adrenergic beta-1 Cardiology and Cardiovascular Medicine business Calcium-Calmodulin-Dependent Protein Kinase Type 2 Signal Transduction |
Popis: | The β-adrenergic receptor (βAR) signaling system is one of the most powerful regulators of cardiac function and a key regulator of Ca2+ homeostasis. We investigated the role of βAR stimulation in augmenting cardiac function and its role in the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) using various βAR knockouts (KO) including β1ARKO, β2ARKO, and β1/β2AR double-KO (DKO) mice. We employed a murine model of left anterior descending coronary artery ligation to examine the differential contributions of specific βAR subtypes in the activation of CaMKII in vivo in failing myocardium. Cardiac inotropy, chronotropy, and CaMKII activity following short-term isoproterenol stimulation were significantly attenuated in β1ARKO and DKO compared with either the β2ARKO or wild-type (WT) mice, indicating that β1ARs are required for catecholamine-induced increases in contractility and CaMKII activity. Eight weeks after myocardial infarction (MI), β1ARKO and DKO mice showed a significant attenuation in fractional shortening compared with either the β2ARKO or WT mice. CaMKII activity after MI was significantly increased only in the β2ARKO and WT hearts and not in the β1ARKO and DKO hearts. The border zone of the infarct in the β2ARKO and WT hearts demonstrated significantly increased apoptosis by TUNEL staining compared with the β1ARKO and DKO hearts. Taken together, these data show that cardiac function and CaMKII activity are mediated almost exclusively by the β1AR. Moreover, it appears that β1AR signaling is detrimental to cardiac function following MI, possibly through activation of CaMKII. |
Databáze: | OpenAIRE |
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