Heart Disease: The Role of PDEs and a PDE Activity Assay
Heart disease is often misunderstood due to confusion with terminology and the different types of heart disease that exist. While a heart attack can occur quickly, heart failure is a slower progression where the heart weakens over time.
One thing is certain; heart disease is the leading cause of death in the United States. 1 Although important; cholesterol levels, exercise, and eating habits are not the only thing we should be concerned with when it comes to heart disease. Anything that stresses the heart has the ability to weaken it.
Some factors are listed here:
- Heart valve disease
- Congenital heart defects
- Irregular heartbeat
- Thyroid disease
- Alcohol overuse
- Lung disease
Targeting Phosphodiesterases in Heart Disease
On a cellular level, the heart muscle and its blood pumping function to keep us oxygenated and alive is extremely complex. At the regulation level, there are enzymes known as phosphodiesterases (PDEs) that degrade second messengers such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These second messengers trigger many cell signaling functions within the body. Specifically, myocardial cells rely on these molecules for a variety of purposes including contraction and relaxation, diastolic stiffness, heart rate, cell growth and survival, interstitial fibrosis, vascular tone, and endothelial permeability and proliferation.2
There are a plethora of ways to treat heart disease. However, each strategy treats a particular symptom and/or cause. Targeting phosphodiesterases is one such strategy. Since PDE3 has been found to regulate cardiac pacemaking and contractility, it’s no surprise that inhibition of PDE3 leads to an increase in heart rate and cardiac contractile ability.3 In fact, there are drugs currently on the market that inhibit PDE3 to improve heart failure. Primacor and Inocor allow for an elevated cAMP pathway that ultimately leads to increased protein kinase A (PKA) activation which further allows for calcium channels to open; thereby increasing cardiac contractility.
How Can A PDE Activity Assay Help?
Even so, more research to understand heart disease on a molecular level, as well as the role of PDEs, is required. BellBrook Labs offers a PDE Activity Assay that can assist scientists in research and drug discovery targeting phosphodiesterases to treat heart disease. These assays can be used to measure enzymatic activity, screen compound libraries for inhibitors, determine inhibitor selectivity, measure inhibitor potency, and inhibitor residence time measurement.
- Control C for D. Centers for Disease Control: Know the Facts About Heart Disease. 2009:1-2. https://www.cdc.gov/heartdisease/facts.htm
- Kim, G. E., & Kass, D. A. (2017). Cardiac phosphodiesterases and their modulation for treating heart disease. In Handbook of Experimental Pharmacology (Vol. 243, pp. 249-269). (Handbook of Experimental Pharmacology; Vol. 243). Springer New York LLC. https://doi.org/10.1007/164_2016_82
- Walter Knight, Chen Yan. Manuscript A. Therapeutic potential of PDE modulation in treating heart disease. 2014;5(14):1607-1620. doi:10.4155/fmc.13.127. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114345/