Abstract
Cardiopulmonary vascular diseases are the leading cause of death worldwide. Metabolic reprogramming and inflammation are 2 commonly shared hallmarks of such diseases. The bifunctional enzymes PFKFB (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases) 1 to 4 are well-known for their critical functions in glucose metabolism. Emerging evidence has indicated that PFKFB enzymes, particularly PFKFB3, are essential immunometabolic regulators and implicated in cardiopulmonary vascular and other pathologies. We here first summarize the structural basis for the catalytic function of PFKFB family enzymes, introduce the recent advances on the regulation of PFKFB3 expression and activity as well as its nonmetabolic functions, then elaborate on how dysregulation of PFKFBs influences physiological and pathological states of the cardiovascular and pulmonary systems, and finally touch on the current development of pharmacological inhibitors of PFKFB3 as potential therapeutics.