Vascular Mechanobiology in Treating Disease

Recent research has suggested that changes in the biological mechanics of the cell are the common denominator in the development of atherosclerosis, aortic valve disease, and aneurysms. The expanding field of mechanobiology, located at the meshing between biology and engineering, focuses on using cellular mechanics rather than the origin and genetics of illnesses to understand the physiology and treat the development of disease.

Cells are constantly under stress and strain from the environment, such as from tensile forces, hydrostatic pressures, and fluid shear stresses. In vascular biology, fluid shear stress helps in the regulation of endothelial cells, which line the walls of blood vessels, by promoting responses that control orientation, gene expression, and vascular tone. An abnormal level of shear stress resulting from disturbed blood flow can lead to diseases like atherosclerosis, characterized by a buildup of plaque inside arteries.

Dr. Hanjoong Jo, the Associate Chair for Emory and a professor of the Coulter Department of Biomedical Engineering, a joint institution between the College of Engineering at the Georgia Institute of Technology and the Emory School of Medicine, conducts research in the expanding field of vascular mechanobiology with a focus on mechanosensitive genes and nanomedicine related to treating atherosclerosis. Specifically, Dr. Jo’s lab studies both in vitro and in vivo models and uses tools such as microarrays to understand genomic functions and the functionality of mechanosensitive genes in the treatment of disease. Investigating atherosclerosis in carotid arteries of mice, the lab members ligated, or clamped shut, different branches of the artery to manually induce disturbed blood flow and used ultrasound to monitor the blood flow and the development of atherosclerosis in each ligated artery. To locate the mechanosensitive genes responsible for this, the team extracted, sequenced and further utilized DNA for epigenetic study: namely, reverse transcription was used to measure levels of gene expression in gene array studies and quantitative PCR validation was run to detect and amplify the resulting RNA. From this, Dr. Jo’s lab discovered that partial carotid ligation causes increased atherosclerosis, which in turn decreases expression of atherosclerosis-preventing genes; in fact, advanced atherosclerosis due to ligation had developed in some mice by the fourth week of the study.

Attempting to understand the causes of atherosclerosis will lead to further research in drug delivery. Currently, drug development is conducted in vivo and uses various small interfering RNA (siRNA) and anti-microRNA to help regulate atherosclerosis-causing genes. However, it is research in fields such as mechanobiology (akin to that being conducted by Dr. Jo) which will allow a different perspective in the development of treatment methods capable of withstanding the harsh conditions of the human body while successfully treating vascular diseases.