David Ford, Ph.D. » Investigators

Cardiovascular Research Interests:

Primary area of research:

• Biochemical mechanisms mediating myocardial ischemic injury
• Macrophage biology and atherosclerosis

Related areas of research:

• Lipid mediated mechanisms mediating obesity-associated metabolic syndrome
• Endothelial dysfunction
• Applied lipidomics in cardiovascular disease, biomarker identification and nutritional studies

Summary of cardiovascular research:

We are interested in the biochemical mechanisms responsible for the pathophysiological sequelae of cardiovascular diseases, including ischemic heart disease and atherosclerosis. Areas of research focus on enzymic and free radical targeting of membrane phospholipids, alterations in lipid metabolism, and alterations in signaling pathways as mechanisms involved in cardiovascular diseases. We combine our expertise using physiological models of disease coupled with expertise in mass spectrometry and bioorganic techniques to identify novel pathways and molecules that may lead to new preventative measures for, and indicators of, cardiovascular disease.

We have shown that plasmalogen phospholipids are targeted by activated phospholipases during myocardial ischemia. Products of these phospholipases activate several signaling pathways, including PKC, PKA, and CREB regulated transcription, which may be critical in myocardial ischemic injury and the salvage of at-risk myocardium. Additionally, we were the first to find that myeloperoxidase-derived, reactive chlorinating species target the vinyl ether bond of plasmalogens resulting in the production of chlorinated fatty aldehydes and unsaturated molecular species of lysophosphatidylcholine. We demonstrated that chlorinated fatty aldehydes are metabolized to chlorinated fatty acids and chlorinated fatty alcohols. Collectively, these novel chlorinated lipids, which we discovered, have been termed the chlorinated lipidome. We have shown that members of the chlorinated lipidome accumulate in response to neutrophil, monocyte, and macrophage activation and their levels increase in ischemic myocardium, atherosclerotic vascular tissue, and as a part of the pro-inflammatory milieu of obesity. Thus, a major emphasis in the Ford laboratory is placed on elucidating the biological roles of these newly-discovered chlorinated lipids in cardiovascular disease and evaluating these lipids as indicators of the progression of cardiovascular disease.

Using lipidomic approaches, we are searching for additional new lipid molecules that have roles in the pathophysiology of cardiovascular disease. In particular, nutritional studies with a focus on the metabolism of saturated fatty acids and trans fatty acids and their role in vascular and heart dysfunction will provide new information on the mechanisms that these fatty acids accelerate cardiovascular disease.