O’Connell Lab for Heart Failure Treatment and Prevention
The focus of the O'Connell lab is to advance the science of heart failure treatment and prevention. One prevailing theory to explain the development and progression of heart failure is hyperactivity of the sympathetic nervous system (SNS). The SNS controls the release of the hormone norepinephrine from nerve terminals, which causes activation of adrenergic receptors leading to cellular response. In heart disease, the activity of the SNS is increased in almost all cases, regardless of the underlying cause of the disease. This hyperactivity is detrimental to the heart, and ultimately leads to cardiac cell death, loss of contractile function, dilation of the heart and death.
Current heart failure therapy is to use a class of drugs known as beta-blockers, which block the action of norepinephrine at beta-adrenergic receptors. Although beta-blockers improve symptoms in heart failure patients, heart failure remains a leading killer in the US, and therefore novel treatments are constantly being sought. In our laboratory, we investigate another type of adrenergic receptor, known as the alpha-1-adrenergic receptor (alpha-1-AR). Using mice in which we have deleted the genes for the subtypes of alpha-1-ARs found in the heart (alpha-1-knockout mice), we demonstrated that alpha-1-ARs are required for postnatal hypertrophy of the heart and for the heart to adapt to stress. In other words, alpha-1-ARs receptors, unlike beta-ARs, play a protective role in the heart.
Our labs investigate the mechanisms by which alpha-1-ARs protect the heart from stress. We will use animal models in which we impose a laboratory model of heart failure in alpha-1-transgenic mice as well as approaches in cardiac cells cultured from alpha-1-knockout mice to study alpha-1-AR function in the heart. The ultimate goal is to determine if an alpha-1-activator would benefit heart failure patients.
Contact Information for O'Connell Lab:
Timothy D. O'Connell, PhD
Associate Scientist and Associate Director, Cardiovascular Health Research Center
Sanford Research/USD
2301 E. 60th Street N
Sioux Falls, SD 57104
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Phone: 605-312-6300
Fax: 605-312-6071
tim.oconnell@sanfordhealth.org |