Hypertension, chronic high blood pressure, is largely a consequence of arterial stiffening, which in turn is caused by processes such as low-level accumulation of cross-links in the extracellular matrix, a form of metabolic waste that our biochemistry cannot effectively remove. One of the many harms done by hypertension is to cause a slow remodeling of portions of the heart, making it larger, weaker, and more prone to failure. The ideal solution to this problem is to remove the root cause - break the cross-links and repair the other forms of cell and tissue damage that degrade the elasticity of blood vessel walls. The medical research community is, as a rule, much more focused on proximate causes and their manipulation, however. So here, researchers identify genes and proteins necessary for the untoward growth and weakening of the heart in response to hypertension - the first step to a treatment that fails to address hypertension, but would diminish one of its consequences. This is the sort of outcome that tends to emerge from restricting the view to proximate causes; just as much time and effort goes into producing a therapy, but the therapy is limited in its scope, and the underlying problem continues on to cause numerous other issues:
Researchers have identified how two proteins, p38 gamma and p38 delta, control the growth of the heart and its adaptation to high blood pressure. The results not only increase our understanding of the mechanisms used by cardiac cells to grow and adapt, but could also help in the design of new strategies to treat heart failure caused by excessive growth of the heart. The heart adapts to the changing needs of each stage of life by adjusting its size. In this way the heart grows in line with the rest of our body, including during pregnancy, in a process called cardiac hypertrophy. However, excessive physical exercise, hypertension, and obesity can trigger excessive heart growth (pathological hypertrophy), a situation that can lead to a heart attack. Understanding the molecular processes that regulate heart function and growth is therefore of immense importance.
The researchers found that p38 gamma and p38 delta regulate the growth of the left ventricle, the largest and strongest heart chamber, responsible for pumping oxygenated blood to the body. The research team showed that the hearts of mice lacking these proteins are smaller than normal. These hearts, although they function normally, are incapable of responding to external stimuli, such as high blood pressure. The discovery advances understanding of the mechanisms through which heart cells grow and adapt. Moreover, "this new information could help in the design of new strategies to combat heart conditions caused by anomalous growth of heart muscle."