Heart disease has a significant role on the death rates in Western countries and is itself caused primarily by stroke or heart attack. The restriction of blood flow to a specific region of the heart and the subsequent loss of tissue oxygenation leads to a heart attack. In the absence of gas exchange, the affected region of the heart undergoes cell death. However, unlike that observed in the damaged liver or skin, the damaged adult heart after a heart attack cannot mount a regenerative response as cardiomyocytes responsible for contractility of the heart cannot re-enter the cell cycle to divide and form new cells. So, because the adult heart cannot self-heal, the destroyed cardiac tissue after a heart attack is replaced by a scar containing the structural protein collagen and this now sick heart has an impaired ventricular activity that will develop into some form of heart disease.
I’ve had the opportunity to work in Dr. Calderone’s lab at the Montreal Heart Institute supervised by his research assistant Vanessa Hertig. Dr. Calderone is a professor in the Dept. of Pharmacology and Physiology at the University of Montreal and his primary area of research is cardiac remodelling after a heart attack. The Holy Grail of cardiac research is identifying the cellular events that will drive cell cycle re-entry of adult cardiomyocytes. To some scientists, the Holy Grail is but a dream. However, Dr. Angelo Calderone’s lab is venturing quite close and the ongoing research is showing overwhelming promise. Work from Dr. Calderone’s lab revealed that, following a heart attack in the rat and human heart, only adult cardiomyocytes bordering the scar express the intermediate filament protein nestin. This data was very interesting because nestin was identified in numerous forms of cancer and directly participates in cell proliferation (cell cycle re-entry) and metastasis. The findings by Dr. Calderone’s lab provided the impetus to assess what cellular events regulate nestin expression and what is the role of nestin in cell cycle re-entry of cardiomyocytes. In vitro data revealed that the drug SB203580 that selectively targets a protein recruited by the inflammatory response (that activated during prior to scar formation) led to nestin expression, and subsequently nestin directly mediated cell cycle re-entry of cardiomyocytes. Therefore, employing SB203580 in vivo may represent a plausible approach to promote the cell cycle re-entry of cardiomyocytes near the border of the scar to partially regenerate cardiac tissue. Indeed, Dr. Calderone’s lab is attempting to determine whether the administration of the drug SB203580 will increase nestin expression and cell cycle re-entry of cardiomyocytes after surgically removing the apex region of a neonatal rat heart. The experiments are ongoing and hopefully a positive result would be obtained.
Why stop there? The applications of cell cycle proliferation are endless, and the next achievable milestone would be neurogenesis and its applications in the exciting world of neuroscience.
Based on my experience in Dr. Calderone’s lab through the Independent Research Project, it is of the utmost importance that young people get involved in ‘real’ science and fundamental research in particular, because:
1. It helps engrave the knowledge obtained from CÉGEP courses into memory through application of the concepts.
2. It provides a perspective of the advantages/disadvantages of a career in a certain domain and provides the requisite knowledge to make a well-weighed decision when it comes to choosing a field of study.
Image Source: Public Domain Pictures
Originally Published in Bandersnatch Vol. 47 Issue 12 on April 11, 2018