Parry Lab: Biology of Relaxin
Welcome to the homepage of the Vascular Physiology, Reproduction, and Aging Group located at the Department of Zoology in The University of Melbourne. Our team investigates the role of the hormone relaxin in a variety of physiological processes including acute heart failure, preeclampsia and aging. The Vascular Physiology, Reproduction, and Aging Group, consisting of 8 staff and students, uses in vivo physiological animal models of human diseases, and molecular biology approaches to answer questions about mechanisms underlying a particular physiology. Specifically we specialise in examination of blood vessel structure and function in response to various genetic and environmental factors.
Our mission is to improve the health and well being of the community through innovative and cutting edge research. We run and extensive research program using rats and relaxin gene knockout mice to establish new functions and mechanisms of relaxin action in reproductive and vascular tissue. In addition we are dedicated to the training of the next generation of scientists to tackle the medical problems of the future.
We published the first data on relaxin receptor expression in arteries, and have recently shown that both vascular smooth muscle cells and endothelial cells express these receptors. These data provided much sought after evidence that relaxin acts directly on blood vessels and causes vasodilation.
Normal pregnancy involves dramatic remodeling of the uterine vasculature, with abnormal vascular adaptations contributing to pregnancy diseases such as preeclampsia. The work of our PhD student, Lenka Vodstrcil demonstrated a functional role for relaxin in mediating uterine artery compliance in pregnant rats, which may be necessary to maintain adequate uterine blood flow to the uterus and placenta. Our current PhD student (Maria Jelinic) and past Honours student (Meghan Richardson) have also made important discoveries in their projects – Rln‐/‐ mice have stiffer mesenteric arteries during their pregnancy and have pups of lower birth weight; there are receptors for relaxin in veins and treatment of male animals with relaxin reduces arterial stiffness.
In 2009‐2012, we received over $1 million in research grants, and established an important collaboration with a leading international pharmaceutical company (Novartis Pharma AG, Switzerland) on a Phase III clinical trial on acute heart failure. We have a major training program for PhD and MSc students in our research group. Our goals are to provide you with unique opportunities to gain practical experience in the laboratory, learn state‐of‐the‐art techniques in vascular physiology and molecular biology, and run your own research project. You will also learn how to present your data, write a major report and publish your results. To date 2 students have successfully completed their Master of Science degree (both H1) and 17 students have completed a BSc (Hons) degree (12 with H1). 60% Hons and 100% MSC/PhD publish data from their thesis and receive national scholarships, the Dean’s Award and international scientific society travel awards and prizes for oral presentations.
1. Regulation of uterine and mesenteric artery function during pregnancy (Parry, Gooi)
Failure of the maternal vascular system to adapt to pregnancy gives rise to serious complications such as gestational hypertension, intrauterine growth restriction and preeclampsia (PE). The cause of these vascular‐related disorders during pregnancy is not well understood. Nevertheless, their pathological origins are thought to occur in the first trimester and are associated with reduced uteroplacental perfusion caused by abnormal uterine vascular remodelling and vasodilation.
- How does relaxin affect uterine and mesenteric artery structure and function in early pregnancy?
- What happens to uterine and mesenteric artery function if pregnant animals do not have relaxin?
2. Placental abnormalities in relaxin gene knock‐out mice (Parry)
Relaxin is also thought to regulate uterine and placental angiogenesis. Relaxin receptors are expressed in the endometrium and placenta in pregnant animals. We recently reported receptors for relaxin in the decidual arteries of early pregnant rhesus monkeys. Therefore, we suggest that relaxin deficiency in early pregnancy impairs vascular remodelling in the placenta and will affect nutrient delivery to the fetus.
- What happens to the placental structure and decidual arteries if pregnant animals do not have relaxin?
3. Novel mechanisms of relaxin action in acute heart failure (Parry, Leo)
From a total of 907,242 deaths occurring in Australia between 1997 and 2003, heart failure was cited as the direct cause of death for 29,341 (3.2%). Data from a Phase II clinical trial in AHF patients demonstrated that when administered with standard‐of‐care therapy, relaxin caused rapid and sustained relief from breathlessness, prevented worsening of heart failure and improved longer‐term outcomes following discharge from hospital. To date, scientists have not been able to provide a complete biological explanation of their findings but have proposed that small resistance arteries are key targets for the actions of relaxin.
The overall aim of this project is to increase our fundamental knowledge on the mechanisms by which relaxin acts on the vascular system to maintain efficient heart function. It provides a unique opportunity to work in collaboration with a pharmaceutical company (Novartis Pharma AG).
- How quickly does treatment with relaxin improve blood vessel structure or function in rats?
- Does relaxin protect against damage to endothelial cells in arteries?
4. Anti‐ageing properties of relaxin‐like peptides in blood vessels (Parry, Jelinic)
Population ageing is occurring on a global scale. The number of people worldwide aged 60 years and over is estimated to triple by 2050, and the population aged 80 years and above is projected to increase more than fivefold. “Global ageing” will place unprecedented demands on societies around the world as older people will want to continue working for longer and actively participate in the community, as well as maintain high quality of life. Blood vessels undergo structural and functional changes with advancing age, including arterial stiffening and thickening, which makes them more susceptible to cardiovascular diseases. How well your arteries perform as you get older depends on complex interactions between lifestyle and genetics. Young mice and rats deficient in relaxin have arteries that are abnormally stiff, synonymous with ageing. This suggests that relaxin plays a role in protecting blood vessels from ageing.
- Is there a change in the functional response to relaxin‐like peptides in mesenteric arteries in response to ageing?
- What mechanisms of action are involved (endothelial dysfunction)?
A/Prof Laura Parry
Office: (03) 8344 4379
Dr Jonathan Gooi
Office: (03) 8344 7040
Dr Chen Leo
Office: (03) 8344 7040
- Dr Marissa Parrott