Coronary microvascular disease (one type of non-obstructive coronary artery disease) and obstructive coronary artery disease (CAD) both reduce coronary blood flow (CBF) and make the heart prone to cardiac ischemia. However, the mechanisms of coronary microvascular dysfunction (CMD)-mediated CBF reduction quite differ from those caused by obstructive CAD. Lipid plaque formation in epicardial coronary arteries (CAs) is the primary reason for reduced CBF in obstructive CAD. In contrast, reduced CBF in CMD is caused by a) increased vasoconstriction and attenuated vasodilation in small distal vessels in the heart, b) decreased capillary density in the heart, and c) coronary arteriole remodeling. CMD not only reduces CBF, but it is also a major cause of heart failure with preserved ejection fraction, resulting in patients’ mortality. Despite these differences between obstructive CAD and CMD, patients with CMD are commonly treated with medications for obstructive CAD, since there is no specific treatment for CMD, and some patients with CMD are not responsive to medications for obstructive CAD. The main focus of our laboratory research is to define the molecular mechanisms of CMD and to develop personalized medicine, or precision healthcare, to treat patients with CMD.
Diabetes is a global epidemic, and close to 14% of the global population has diabetes. Patients with diabetes develop cardiovascular disease, and diabetes is ranked the 7th leading cause of death in the U.S. Diabetic heart diseases include diabetic cardiomyopathy, obstructive CAD, and CMD. Importantly, CMD significantly increases cardiac mortality in patients with diabetes. Therefore, there is an urgent need to understand the molecular mechanism by which diabetes leads to CMD and develop effective treatments for diabetic patients with CMD. During the past 20 years, we have made significant contributions to understanding the mechanisms of diabetes-mediated CMD.
Among patients who experienced chest pain, more than 50% of women had CMD instead of obstructive CAD. On the other hand, only 20% of men with chest pain had CMD. In addition, the majority of patients with CMD are at the age of 50 or older. The average age of menopause is 51 in the U.S., implying that female patients are most likely in the perimenopause or postmenopause stage. Therefore, we investigate whether menopause is an independent risk factor for CMD and define the molecular mechanisms by which menopause leads to CMD.