For Immediate Release: Media Contact:
May 1, 2008 Julie Jette
617-636-3265
jjette@tuftsmedicalcenter.org
Tufts Medical Center Researchers Identify a
New Mechanism for High Blood Pressure
Study finds that blood vessel abnormalities, not just kidney abnormalities, can cause hypertension
Boston, MA – Researchers at Tufts Medical Center have demonstrated that abnormalities in blood vessels – rather than only kidneys, as has been previously thought – can act as a primary cause of high blood pressure.
This research, published in the Proceedings of the National Academy of Sciences, could lead to new ways to attack the disease, which afflicts an estimated 65 million Americans, leaving them at higher risk for heart attack, stroke and other life-threatening health problems. The findings are significant for the 90 to 95 percent of hypertensive individuals whose high blood pressure is not linked to a specific cause.
“These results suggest a potential paradigm shift in the field of hypertension. Previously, all causes of hypertension were thought to arise from the kidney, but that assumption was based on extremely rare genetic causes that do not pertain to the vast majority of patients with high blood pressure,” said Howard K. Surks, MD, a Tufts Medical Center cardiologist and co-author of the study. “Our data suggest that an abnormality in the blood vessel that does not affect kidney function can also cause high blood pressure. This validates efforts to find new targets for the treatment of hypertension in the blood vessel.”
Researchers genetically engineered mice to produce a slightly altered form of a protein called PKG, which occurs naturally in the body and helps to relax smooth muscle cells in blood vessel walls. PKG does this by enhancing the activity of an enzyme located inside the cells of the blood vessel. This enzyme enables “muscle fibers” inside those cells to relax - thereby allowing the blood vessel walls to dilate, and lower blood pressure. The altered form of PKG did not interact normally with the enzyme, and the study found the breakdown in this molecular-level communication system led to hypertension in the specially engineered mice. Extra care was taken in the study to examine the kidney function of the mice to rule out renal causes of high blood pressure: the mice in the study did in fact have normally-functioning kidneys.
As with normal mice, healthy human blood vessels contain PKG, which enables their blood vessels to dilate properly to lower blood pressure. When blood vessels cannot dilate sufficiently as blood circulates through the body, blood pressure increases, leading to a host of medical problems, including stroke, heart attacks, kidney failure and heart failure.
“In a very real sense, the single cell layer which lines all blood vessels in the human body, the endothelial cell layer, can be thought of as an organ system in its own right.” said Simon K. Michael, MD, PhD., a neonatologist at Floating Hospital for Children at Tufts Medical Center, and co-author of the paper. “Our experiments have disrupted an important communication pathway between the endothelial cell and the underlying cells of the blood vessel wall. Our results suggest that dysfunction in this system may well be an important underlying cause of cardiovascular disease in humans. In retrospect, this seems quite intuitive.”
The induction of high blood pressure by creating a blood vessel defect in mice raises the intriguing possibility that there are blood vessel abnormalities that cause high blood pressure in people. The researchers at are now looking at human DNA to determine whether abnormalities in PKG or other related blood vessel proteins may exist in people with high blood pressure.
An abstract of this paper can be found at:
http://www.pnas.org/cgi/content/abstract/0802128105v1.
Simon K. Michael*, Howard K. Surks*, Yuepeng Wang*, Yan Zhu*, Robert Blanton*, Michelle Jamnogjit*, Mark Aronovitz*, Wendy Baur*, Kenichi Ohtani*, Michael K Wilkerson**, Adrian D. Bonev**, Mark T. Nelson**, Richard H. Karas*, and Michael E. Mendelsohn*
*Molecular Cardiology Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston MA 02111; and **Department of Pharmacology, University of Vermont, Burlington VT 05405