Below is a summary of Jennifer Bryant’s discussion about cardiac remodeling in last wee’s Suter Science seminar. Enjoy!

Jennifer Bryant, who is an associate professor in biopharmaceutical sciences at Shenandoah University, gave a lecture about the research she has performed over the last decade that concerns cardiac remodeling and fibrosis occurring after someone has a heart attack. Although there are a variety of cardiovascular diseases, Bryant primarily focuses on heart problems that stem from coronary heart disease, including stable angina pectoris, unstable angina pectoris and myocardial infarctions (heart attacks). Cardiovascular disease remains an important topic because this disease is the number one killer of humans, both globally and in the United States. A fact that I did not know about cardiovascular disease is that it kills more humans than all forms of cancer. As mentioned previously, a great deal of Bryant’s research concerns myocardial infarctions, which is an acute coronary syndrome arising when a section of the heart’s circulatory system is blocked, subsequently causing cardiac cells to die from lack of oxygen. Typically, blockage of circulation is caused by a thrombus (blood clot) in the blood vessels and in addition, loss of blood flow will cause ischemia and cell death.

The heart responds to a myocardial infarction in a number of ways. First, tissues in the heart called myocytes die and are no longer able to proliferate. Second, the death of myocytes in the heart triggers an inflammatory response. Third, another type of tissue in the heart called fibroblasts begins to proliferate and secrete proteins from the extracellular matrix that forms a scar on the heart. The cardiomyoctes that are healthy and viable will grow in size in order to compensate for the loss of myocyte tissue due to the myocardial infarction. Finally, the heart will experience heart failure at some point in the future, because it has worked so hard to overcompensate for the dead myocyte tissues. This entire process of repair that the heart undergoes is called cardiac remodeling. Bryant and her colleagues wanted to see if there was a way to help the heart from succumbing to heart failure in the end after sustaining significant damage.

Cardiac fibroblasts, which are small in size, are the major non-contractile cell in the heart and make up 2/3 of cells in the heart. In addition to being able to proliferate, these cells are also able to differentiate into myofibroblasts. Myofibroblasts are a subtype of fibroblast cells that are able to secrete large amounts of extracellular matrix proteins. These cells are only present during wound healing and eventually die after secreting these proteins, however issues can arise if the myofibroblasts do not die and continue secreting extracellular matrix (ECM) proteins. By using immunofluorescence and Western Blotting methods during in vivo experiments involving rats, Bryant was able to begin discerning how the ECM affects differentiation and how the ECM composition is altered after a myocardial infarction. Results revealed that collagen type VI, a minor form of a collagen isoform in the heart, is involved in myofibroblast differentiation. Collagen VI is composed of three alpha chains containing large globular proteins located at the end of the chains. Following an MI, there is an increase of collagen VI fibers in the heart 20 weeks after an infarction in rats. From these results, Bryant and her colleagues proposed another question: does the increase of collagen VI fibers cause differentiation myofibroblasts in the post-infarction heart? They found that at 7 days and at 20 weeks, the increase of collagen gives rise to differentiated myofibroblasts, which means that they disappear after about a week (during the inflammatory response) and return again down the road. Although Bryant does not go into much detail about possible mechanisms for the disappearance and reappearance of myofibroblast differentiation, she briefly suggests the possibility of receptors that may be responsible for attaching collagen VI to cardiac fibroblasts.

From the knowledge Bryant and the rest of her colleagues have gleaned from their studies, they have begun new research to try and gain answers to the following questions: 1) are there any genetic alterations that may increase the risk of an MI and 2) are there any single nucleotide polymorphisms (SNPs) in type VI collagen that would increase the risk of an MI? A polymorphism is one specific genetic change that occurs commonly in the population. A SNP is different from a mutation because mutations are less common and more likely to cause a disease then SNPs. In this new current study, Bryant and colleagues focused on a population of individuals who have been admitted to the hospital more than once for an acute coronary syndrome (ACS). Buccal swabbing was performed on these participants in order to obtain their DNA, which would be compared to the control group (those without a history of ACS). PCR analysis was used to amplify the DNA that was obtained in order to observe for the presence of SNPs and other specifics of the genetic material. Some of the SNPs, particularly SH2B3 and COL6A1, have been found in past experiments to be associated with a variety of cardiovascular diseases, including MIs. Because this experiment is not yet complete, Bryant was not able to provide conclusions for the questions posed earlier, however I am interested to know what the results will ultimately reveal. Furthermore, perhaps these pending results will be able to provide some insight in the future on creating prevention methods for those who are found to have SNPs that may increase the risk of some cardiovascular diseases.