Dr. Grant Pierce
– Cell Biology

Dr. Grant Pierce
Principal Investigator, Cell Biology Laboratory
Institute of Cardiovascular Sciences

Research Focus

There are currently 4 research selections being followed within our laboratory:

1) We are interested in the role that dietary flaxseed may play in providing significant benefits to our cardiovascular health. We have initiated several studies investigating the effects of flaxseed on cardiovascular performance in animals. We are continuing to investigate its effects in humans in both healthy populations and in those with clinical symptoms of cardiovascular disease.

2) We are interested in the role of sodium calcium exchange in ischemia reperfusion injury. Using molecular approaches to increase or decrease the expression of the sodium calcium exchanger, we continue a long standing interest in understanding the ionic basis of ischemic reperfusion damage to the heart.

3) We are interested in the role of infection and inflammation on cardiovascular disease. Specifically, we examine how infectious agents like Chlamydia pneumonia may promote atherosclerosis in in vitro and in vivo models.

4) We are interested in the factors that regulate nuclear protein import in vascular smooth muscle cells. The movement of proteins into the nucleus represents signaling information that can influence cell growth. We are interested in the processes that regulate this signaling during healthy development and during disease conditions.

Why is this work important?

Our work investigates the basic mechanisms that may be responsible for modifying, inducing or preventing cardiovascular disease. Our research is unique in that it attempts to go from bench to bedside in a number of studies employing not only cell biology and molecular biology techniques to improve our understanding of cardiovascular health, but also dietary interventions to delay or prevent the development of cardiovascular disease processes.

What techniques and equipment are used in this laboratory?

We have a basic cell biology laboratory that employs many different biochemical and molecular biology techniques to obtain information. This includes the use of adenoviruses, siRNA, cell culture, organ culture, tissue perfusion in both vascular tissue, cardiac muscle and adipose tissue. We routinely use gel electrophoresis, western blots, northern blots, HPLC, GC, langendorf and tissue perfusion of arterial rings and isolated hearts, as well as a variety of other techniques.

About Dr. Grant Pierce

Dr. Grant Pierce has published ~200 manuscripts that have attracted more than 4000 citations. His past work focused on the identification of a cardiomyopathy in diabetes and on Na/H exchange as an important mechanism responsible for ischemic heart disease. He is currently interested in nuclear protein import as a mechanism for cell growth in the cardiovascular system, on the relationship of infection and inflammation with atherosclerosis, and on the potential for nutraceuticals and functional foods to alter cardiovascular disease. He is the Executive Director of Research at St Boniface General Hospital and Co-Editor of the Canadian Journal of Physiology and Pharmacology.

For more information, please contact:

Grant N. Pierce, PhD, FACC, FAHA, FISHR, FAPS, FIACS
Executive Director of Research, St. Boniface General Hospital
Professor of Physiology and Pharmacy
University of Manitoba

Phone. 204.235.3206
Fax. 204.235.0793
Email. gpierce@sbrc.ca

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In Detail

Searching for the key to the clog in arteries

The majority of deaths from heart failure and stroke – some 70% — are due to atherosclerotic blockage. “We knew for many years there was a great correlation between cholesterol and LDL and heart disease,” Dr. Pierce explains. “Problem was, in a cell culture in our laboratory we couldn’t reproduce that at all. There had to be something missing.” The missing link, Dr. Pierce discovered, was the oxidized form of LDL – low-density lipoprotein. This oxidized LDL is now a major focus of his laboratory’s studies.

Understanding the interactions that lead to blockage

Lipoproteins are proteins that attach to cholesterol to transport it through the bloodstream. Low density lipoprotein (LDL), know popularly as the “bad” cholesterol, carries cholesterol from the liver to body tissues while high density lipoprotein (HDL) is believed to extract and transport some of the excess cholesterol from tissues back to the liver where it is broken down and excreted. The cholesterol attached to LDL has long been recognized as a primary source of fatty deposits in blood vessels.

Atherosclerosis is known as “hardening of the arteries” because, in atherosclerotic plaque, calcium increases about 100-fold. This creates a situation in which a normally distensible, compliant artery literally becomes hard. It no longer has the capability to regulate the flow of blood according to the body’s needs. In addition, the muscle cells that surround the artery and are responsible for squeezing or relaxing it are no longer able to function optimally. These cells fill with cholesterol, then begin to regenerate and move inside the vessel, building up the plaque that slows or even blocks the flow of blood.

As Dr. Pierce discovered, simply adding LDL to cells in culture did not cause them to fill with fat. However, when the LDL was oxidized with free radicals, it suddenly flowed into the cells in great quantities. His laboratory is investigating how the oxidized LDL changes the cell to allow excessive calcium into it and how it influences the way the cells move and proliferate to create vessel blockage. Once the key to these occurrences is understood, it may be possible to determine ways of preventing them, through drugs or other means. This research will have important implications for understanding the mechanisms responsible for ischemic stroke and heart attacks.

Insights into diabetic heart disease

Diabetics have a much higher incidence of heart disease than the general population. Dr. Pierce has studied insulin-deficient animal models that are similar to juvenile onset diabetes in humans, and learned how the heart works over in these animals. Recently, an animal model for Type II or adult-onset diabetes has been developed, providing an opportunity to compare the two. In Type II diabetes, insulin levels are normal or high and the animal model being used in the study demonstrates high levels.

To date, major differences in heart function have been discovered between the two different models. Data, which is still being gathered and assessed, suggest that insulin is the factor that is creating the differences. This could have broad implications for the study of heart disease in the future.

Top

2010

1. Ander, B.P., Edel, A.L., McCullough, R., Rodriguez-Leyva, D., Rampersad, P., Gilchrist, J.S.C, Lukas, A. and Pierce, G.N. Distribution of omega-3 fatty acids in tissues of rabbits fed a flaxseed-supplemented diet. Metabolism, 59: 620-627, 2010.

2. Bassett, C.M.C., Edel, A.L., Patenaude, A.F., McCullough, R.S., Blackwood, D.P., Chouinard, Y., Paquin, P., Lamarche, B., Pierce, G.N. Dietary vaccenic acid has anti-atherogenic effects in LDL r-/- mice. J. Nutr., 140: 18-24, 2010.

3. Maddaford, T.G., Dibrov, E., Hurtado, C., and Pierce, G.N. Reduced expression of the sodium-calcium exchanger in adult cardiomyocytes via adenovirally delivered shRNA results in resistance to simulated ischemic injury. Am. J. Physiol., 298: H360-H366, 2010.

4. Rodriguez-Leyva, D., Dupasquier, C.M.C., McCullough, R. and Pierce, G.N. The omega-3 fatty acid alpha linolenic acid within flaxseed provides beneficial cardiovascular effects. Can. J. Cardiol., 26: 489-496, 2010.

5. Deniset, J.F., Cheung, P.K.M., Dibrov, E., Lee, K., Steigerwald, S., and Pierce, G.N. Chlamydophila pneumoniae infection leads to smooth muscle cell proliferation and thickening in the coronary artery without contributions from a host immune response. Am. J. Pathol., 176: 1028-1037, 2010.

6. Rodriguez-Leyva, D., and Pierce, G.N. The cardiac and haemostatic effects of dietary hempseed.Nutr. Metab., 7:32-41, 2010.

7. Gilchrist, J.S.C., Cook, T., Abrenica, B., Rashidkhani, B., and Pierce, G.N. Extensive autolytic fragmentation of membranous versus cytosolic calpain following myocardial ischemia/reperfusion. Can. J. Physiol. Pharmacol., 88: 584-594, 2010.

8. Clark, T.A., Maddaford, T.G., Tappia, P.S., Heyliger, C.E., Ganguly, P.K., and Pierce, G.N. Restoration of cardiomyocyte function in streptozotocin-induced diabetic rats after treatment with vanadate in a tea decoction. Curr Pharm. Biotechnol. 11:906-910, 2010.

9. Xu, B., Zhou, Y., O, K., Choy, P.C., Pierce, G.N. and Siow, Y.L. Regulation of stress-associated scaffold protein J1P1 and J1P3 on the c-Jun NH2-terminal kinase (JNK) in ischemia/reperfusion. Can. J. Physiol. Pharmacol. 88:1084-1092, 2010.

10. Deniset, J.F. and Pierce, G.N. The value of therapeutic interventions in disrupting Chlamydophila pneumoniae involvement in cardiovascular disease. Fundamental Clin. Pharmacol., 24:607-617, 2010.

11. Zettler, M.E., Merchant, M.A. and Pierce, G.N. Augmented cell cycle protein expression and kinase activity in atherosclerotic rabbit vessels. Exp. Clin. Cardiol., 15:e139-e144, 2010.

2009

1. Chahine, M.N., Blackwood, D.P., Dibrov, E., Richard, M.N., and Pierce, G.N. Oxidized low density lipoprotein affects smooth muscle cell growth through MAPK-mediated actions on nuclear protein import. J. Mol. Cell. Cardiol., 46: 431-441, 2009.

2. Bassett, C.M.C, McCullough, R.S., Edel, A.L., Maddaford, T.G., Dibrov, E., Blackwood, D.P., Austria, J.A., Pierce, G.N. Trans fatty acids in the diet stimulate atherosclerosis. Metabolism, 58: 1802-1808, 2009.

3. Rodriguez-Leyva, D., McCullough, R. and Pierce, G.N. Nutrition as a vehicle for cardiovascular translational research. J. Cardiovasc. Translational Res., 2: 328-334, 2009.

4. Chahine, M.N., and Pierce, G.N. Therapeutic targeting of nuclear protein import in pathological cell conditions. Pharmacol. Rev., 61: 358-372, 2009.

5. Bassett, C.M.C., Edel, A.L., Patenaude, A.F., McCullough, R.S., Blackwood, D.P., Chouinard, Y., Paquin, P., Lamarche, B., Pierce, G.N. Dietary vaccenic acid has anti-atherogenic effects in LDL r-/- mice. J. Nutr., 140: 18-24, 2010.

6. Maddaford, T.G., Dibrov, E., Hurtado, C., and Pierce, G.N. Reduced expression of the sodium-calcium exchanger in adult cardiomyocytes via adenovirally delivered shRNA results in resistance to simulated ischemic injury. Am. J. Physiol., 298: H360-H366, 2010.

7. Rodriguez-Leyva, D., Dupasquier, C.M.C., McCullough, R. and Pierce, G.N. The omega-3 fatty acid alpha linolenic acid within flaxseed provides beneficial cardiovascular effects. Can. J. Cardiol., 26:489-496, 2010.

8. Deniset, J.F., Cheung, P.K.M., Dibrov, E., Lee, K., Steigerwald, S., and Pierce, G.N. Chlamydophila pneumoniae infection leads to smooth muscle cell proliferation and thickening in the coronary artery without contributions from a host immune response. Am. J. Pathol., 176: 1028-1037, 2010.

9. Rodriguez-Leyva, D., and Pierce, G.N. The cardiac and haemostatic effects of dietary hempseed. Nutr. Metab., 7:32-41, 2010.

10. Faustino, R.S., Maddaford, T.G. and Pierce, G.N. Mitogen activated protein kinase at the nuclear pore complex. J. Cell. Mol. Med., in press, 2010.

11. Clark, T.A., Maddaford, T.G., Tappia, P.S., Heyliger, C.E., Ganguly, P.K., and Pierce, G.N. Restoration of cardiomyocyte function in streptozotocin-induced diabetic rats after treatment with vanadate in a tea decoction. Curr Pharm. Biotechnol. 11:906-910, 2010.

2009

Outstanding Leadership in Health Research Award from the Life Sciences Association of Manitoba.

2010

Manjeet Singh Oration Award for outstanding contributions in cardiovascular sciences from the Joint International Conference of the International Society for Heart Research and the International Academy of Cardiovascular Sciences, Indian Section, New Delhi, India.

2010

Jan Jessenius Gold Medal in Medical Sciences from the Slovak Academy of Sciences, Bratislava, Slovakia in recognition of outstanding international achievement in the field of medical research.

1. CIHR Operating Grant on “The Effects of Specific Fatty Acids on Cardiovascular Health”

2.CIHR Operating Grant on “Nuclear Protein Import in Vascular Smooth Muscle Cells”

3. Flax2015 Operating Grant on “Dietary flaxseed to control symptoms of cardiovascular disease in patients with peripheral arterial disease”

4. Agri-food Research and Development Initiative Operating Grant on “Dietary flaxseed to control symptoms of cardiovascular disease in patients with peripheral arterial disease”

There are no opportunities available at this time.