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
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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