Coronary Microvascular Disease in Diabetes: Role of NAMPT
Abstract
Fiscal Year 2020 PRMRP Topic Area: Diabetes and Women’s Heart Disease. In the United States, more than 34 million people suffer from diabetes (a disease in which your blood sugar level is too high). The Department of Veterans Affairs (VA) reported that approximately 25% of VA patients are diagnosed with diabetes. Uncontrolled sugar levels in your blood increase the risk of vascular abnormality (including high blood pressure, coronary artery disease, and stroke), nerve damage, vision loss, kidney failure, and amputations. Diabetes is the seventh leading cause of death in the United States; nearly 65% of individuals with diabetes die from the complication of diseases related to the heart or blood vessels. Diabetic patients have a greater likelihood of suffering from chest pain due to narrowed vessels in the heart by a buildup of plaque (fatty deposits), termed obstructive coronary artery disease. Besides, recent studies shed light on the importance of chest pain induced by abnormal function of small distal vessels (microvascular) in the heart, called coronary microvascular disease (CMD). The evidence also shows that diabetes is an independent risk factor for CMD. However, little is known about how diabetes leads to CMD. CMD is primarily caused by the abnormal function of endothelial cells, which line the inner layer of blood vessels. EC has the ability to form tiny blood vessels (capillary) and also relax blood vessels. Patients with diabetes show decreased capillaries in the heart and attenuated relaxation of blood vessels. This study is designed to identify the molecular mechanisms by which high sugar level in the blood leads to the defect of endothelial cells in the heart of diabetic patients. Among patients who experienced chest pain, more than 50% of women have CMD instead of obstructive coronary artery disease, whereas 20% of men with chest pain have CMD. Therefore, we will also investigate the effect of gender differences on the development of CMD in diabetes. Nicotinamide phosphoribosyltransferase (NAMPT) is a protein found in the blood, and it has two major functions: an initiator of inflammation and a producer of the energy. The protein concentration of NAMPT is increased in the blood of diabetic patients; however, it has never been investigated whether the upregulation of NAMPT is implicated in the defect of small vessels of the heart in diabetic patients. We will thus study the effect of NAMPT in the development of endothelial dysfunction in the heart and CMD in diabetes by using the gain- and loss- of function approaches. This study bears significant clinical relevance to the prevention and treatment of cardiovascular complications of diabetes, a disease suffered by 25% of Veteran patients. Completion of this study will provide important insights into the development of the precision health science approach to defining the novel and right treatment for diabetic patients with CMD.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110472
Entities
People
- Ayako Makino
Organizations
- United States Army
- University of California, San Diego