Part 1: BASIC FOUNDATIONS OF CARDIOLOGY Chapter 4:
PRINCIPLES OF MOLECULAR CARDIOLOGY Author: Robert Roberts
Application of the techniques of recombinant DNA to cardiovascular disorders appears to be essential and appropriate to overcome several of the major obstacles to immediate and future progress.1-3 The heart exhibits three characteristic adaptive responses to changes in its environment: the constitutive adaptive mechanism-namely, myofibril stretch that regulates cardiac output on a beat-to-beat basis (Starling's law)4; modulation of excitation contraction coupling through intramyofibril calcium leading to increased heart rate and force of contraction; and the long-term adaptation of compensatory growth (see Chap. 5). The first two adaptations were characterized extensively in the 20th century through the development, refinement, and application of hemodynamic techniques. In the 21st century, the molecular basis for the growth response will be elucidated and will include deciphering the basis for cardiac differentiation and development. This will be necessary if one desires to therapeutically modulate growth. Similarly, elimination of restenosis after angioplasty probably will require disruption of smooth muscle migration and proliferative response.5 Unraveling the molecular basis of hereditary cardiac disorders is well underway, and with completion of the Human Genome Project within the next couple of years, this will be accelerated considerably6,7 (see Chap. 62).
We have already entered the era of genetically engineered drugs such as recombinant tissue plasminogen activator (rt-PA),8 which initiated a paradigmatic shift in the therapy of myocardial infarction, resulting in an acute mortality of only 6 percent.9 The era referred to as pharmacogenomics is rapidly approaching, in which therapy will be individualized on the basis of a patient's genotype.10
Was this article helpful?