A Research headed by the vascular surgeon Rajabrata Sarkar, MD, PhD, at the San Francisco VA Medical Center has unraveled the genetic mechanism that helps in the growth of new arteries . He demonstrated in mice that the MMP2 gene is the key factor for the development of new arteries especially when there is blockage in the femoral (leg) artery.
As a novel approach the team has analyzed and given detailed information on the DNA sequence of the MMP2 gene, which encodes an enzyme believed to promote the growth of new arteries. This can be found in the November 8 issue of the Proceedings of the National Academy of Sciences.
Understanding the development of new arteries is very essential because when there is an insufficient blood flow to the leg, it can lead to gangrene, necessitating leg amputations under worse conditions.
Sarkar and his researchers (University of California, San Francisco) conducted a study in which two sets of mice were taken and human vascular disease was mimicked in the femoral arteries in both the sets, normal mice having the intact gene and the other lacking the MMP2 gene. In about three weeks, the normal mice developed new arteries and the blood flow was restored close to normal levels. In the other set of mice that lacked MMP2 gene, new arteries failed to grow and 40% of these lost a part of their leg as a result of gangrene. This shows that the gene is vital for the growth of new arteries when there is blockage.
The research team also studied accurately those areas of the MMP2 gene that were activated in skeletal muscles when there was a decrease in the blood flow. The transgenic mice created, by David Lovett, provided a representation of the arterial blockage.
The beta galactosidase gene marker was incorporated into the transgenic mice, which turns tissues blue. Different strains of the mice had different fragments of the MMP2 gene linked to the marker gene. When there is an arterial blockage in the strain of mice with the specific gene sequence, the leg muscles turn blue. Hence this paved way for the researchers to specifically spot new areas within the MMP2 gene and other adjuvant molecules that are necessary for the expression of the gene during decreased blood flow.
As it is a fundamental approach to understand the pathway of the gene involved in the growth of arteries, further research has to be done to understand the various conditions like cigarette smoking, high cholesterol, diabetes, and hypertension in relation with vascular diseases according to the researchers.
The research teams intend to study the same genetic mechanisms in humans, with the tissue samples taken from patients during surgery. It is hoped that this research would eventually pave way for the development of novel treatment modalities towards 'curing' patients with arterial blockage.