Contact info

Dr Julie L. Lavoie
CRCHUM � Pavillon R
900, Saint-Denis � Room R08.452
Montreal, QC H2X 0A9

Tel: 1-514-890-8000, ext. 23612
E-mail: [email protected]

Research keywords

Julie L. Lavoie was trained in Exercise Physiology in the Department of Kinesiology at the Universit� de Montr�al where she obtained a PhD degree. Her thesis was in the field of sympathetic nervous system regulation during muscle contraction under the supervision of Dr Louise B�liveau. She then joined Dr Curt Sigmund's laboratory at the University of Iowa, where she worked as a post-doctoral fellow on the implication of brain and kidney renin-angiotensin system in hypertension. She was recruited in 2004 by the CHUM research center as a researcher and became a Research Assistant Professor in the Department of Medicine at the Universit� de Montr�al the next year. Her research focuses on the effect of exercise training on the development of preeclampsia as well as the implication of adipose tissue renin-angiotensin system in the development of obesity and its related diseases using animal models of these pathologies.

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1. Pathophysiological role of local RASs. Over the past decade, local renin-angiotensin systems (RASs) have been found to have profound effects on blood pressure (BP) and fluid homeostasis. For instance, it has been reported that the brain RAS might be implicated in the development of hypertension. However, the effects of renin in the brain are still very controversial, since it is present in such low concentrations. Employing a novel transgenic model, we were able to identify renin-specific nuclei and cell types (glial or neuronal) (Physiol Genomics 16:240-6, 2004), thereby shedding light on this unresolved problem. In addition, we identified certain cells or microdomains that contained both renin and angiotensinogen (AGT) (Hypertension 43:1116-9, 2004). These experiments revealed the existence of brain-specific nuclei that may be implicated in the Ang-II regulation of BP and fluid homeostasis. In addition, although an alternative form of renin has been found in the brain, studies had failed to identify its physiological role. We produced a transgenic mouse model that expresses this alternative form of human renin, specifically in brain glia. We established that when these mice are bred with mice that express human AGT, also in glia, the resulting double transgenic mice are mildly hypertensive and manifest a significant increase in drinking (Hypertension 47:461-6, 2006). To the best of our knowledge, this study is the first to demonstrate a physiological role for this form of renin. The renal RAS has also been implicated in the development of hypertension. Thus, we produced another transgenic model to investigate the role of the RAS in kidney proximal tubules. We demonstrated that increased production of Ang-II, specifically in proximal tubules, causes significant BP elevation (Am J Physiol Renal Physiol 286:F965-71, 2004), implicating the kidney RAS as a mechanism for the development of hypertension.

2. Novel, clinically-relevant mouse models of stroke and preeclampsia. Although the stroke-prone spontaneously-hypertensive rat has been enormously useful as an experimental model of stroke in studies of the cerebral circulation, these animals usually have ischemic strokes, which are uncommon in patients with hypertension. We were able to describe the first model of spontaneous hemorrhagic stroke, in hypertensive mice (Stroke 36:1253-8, 2005). Furthermore, the type and locations of their strokes are reasonably similar to those observed in clinical hypertension. Indeed, double transgenic mice � which overexpress human renin and human AGT (R+A+) � when administered both a high-salt diet and L-NAME, died of hemorrhage in the brainstem within 10 weeks, and several mice also presented with hemorrhage in the cerebellum and basal ganglia. We also recently characterized a novel model of preeclampsia superimposed on hypertension. We established that female R+A+ mice develop de novo proteinuria and have a significant increase in BP (around 30 mmHg) during pregnancy, which is associated with cardiac pathology, intrauterine growth restriction and increased circulating and placenta sFlt-1 (Hypertension 54:1401-7, 2009). To our knowledge, this is the first model of this clinical reality, and it will be of significant use in determining the mechanisms implicated in this disease as well as in evaluating novel treatments.

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Current projects in the laboratory fall into two areas:

Preeclampsia animal models and impact of exercise training. This project studies preeclampsia, a pregnancy-associated disease in which women develop hypertension and proteinuria, and the effect of exercise training on the pathology in animal models. Furthermore, we wish to investigate the mechanisms by which exercise training can prevent the disease.

Adipose renin-angiotensin system and obesity and obesity-related disease. We wish to investigate the implication of the local renin-angiotensin system (RAS) in adipose tissue on obesity and obesity-related diseases such as hypertension and diabetes. For instance, we will evaluate the involvement of the renin receptor in the development of obesity and its related symptoms as well as investigate the potential therapeutic value of the renin receptor blocker for the treatment of obesity and the metabolic syndrome. Also, with the use of novel transgenic mice, we plan to determine which RAS inhibitor, when comparing renin and angiotensin converting-enzyme inhibitors as well as angiotensin receptor blockers, may be more effective for the treatment of hypertension-related to obesity as these individuals are presently difficult to treat.

The laboratory addresses these investigations using a wide array of physiology, molecular biology and animal phenotyping technologies including EchoMRI, echocardiography, mouse transgenic and KO models, vascular reactivity on isolated vessels, blood pressure telemetry, real-time PCR, western blot, etc.