MedicalResearch.com Interview with:
Sakthivel Sadayappan, PhD, MBA
Associate Professor Department of Cell and Molecular Physiology
Loyola University Chicago Health Sciences Division
Maywood, IL 60153-5500, USA.
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Sadayappan: Hypertrophic cardiomyopathy (HCM) is the most common form of genetic heart defect, affecting 1 in 500 people in the general population. HCM results in excessive thickening of heart muscle without an obvious cause, such as hypertension or exercise stress. Often, HCM results in sudden cardiac arrest as a result of cardiac arrhythmia. Electrocardiogram, echocardiogram and cardiac magnetic resonance imaging are commonly used to diagnose HCM. However, genetic defects in more than 10 genes could also cause HCM, and standard screening for these genes is readily available. Notwithstanding our ability to diagnose the disease, a major challenge arises from its heterogeneity. That is, individuals with the same genetic defect often present with different symptoms, ranging from no symptoms at all to severe heart enlargement. Therefore, treatment options vary from person to person, and, at present, no permanent cure is available for HCM. Beta-blockers, calcium antagonists and anti-arrhythmic drugs are currently being used to manage the disease. However, scientists must discover the reasons that explain why some people experience more severe symptoms than others.
In today’s modern world, people are afflicted with stresses including, for example, diabetes, hypertension, hyperlipidemia (high cholesterol), and alcoholism. Therefore, we have hypothesized that additional cardiac stresses can aggravate the onset of Hypertrophic cardiomyopathy. To prove our hypothesis, we used a mouse model having a genetic defect known to affect cardiac muscle contractility. We subjected these mice to severe cardiac stress over a period of 12 weeks. Compared with normal mice, we found that the mutant mice showed significant cardiac abnormalities, including those associated with
HCM. Thus, this demonstrated, for the first time, that additional cardiac stress applied in the presence of known genetic defects exacerbates the onset of HCM.
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MedicalResearch.com Interview with:
Anna Geraghty
Department of Integrative Biology
University of California, Berkeley, Berkeley,
Medical Research: What is the background for this study? What are the main findings?
Response: RFRP3 in mammals has been well characterized as a negative regulator of the hormonal reproductive axis. It shuts down release of gonadotropins necessary for successful reproduction, similar to how stress inhibits reproduction. Our lab has previously shown that stress can directly regulate RFRP3 levels in males-both acute and chronic stress lead to an upregulation of RFRP3 levels in the male rat. As a followup to that study, we were interested in looking at whether this response was similar in females, and how that may affect long term fertility. We found that chronic (18 days) of stress led to an increase in RFRP3 levels all all stages of the estrous cycle. This increase was also sustained for at least 4 days, or one whole estrous cycle, after the stress ended- the equivalent to a month menstrual cycle in humans. In rats that were stressed and then allowed to recover for 4 days, animals that were stressed were significantly less successful at reproducing- 76% success rate in controls compared to 21% in the stressed animals. This was a result of a combination of deficits in the mating process- less stressed animals successfully copulated, those that did successfully mate had fewer pregnancies, and gave birth to smaller litters. However, utilizing an inducible virus to knockdown RFRP levels in the hypothalamus specifically during the stress period prevented all of these problems- stressed animals without stress-induced RFRP3 increases looked indistinguishable to controls.
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