Table 1.

Recent advances in treating obesity-induced ED.

Potential targets/interventions		Effects and mechanisms
Single-target	EC (29)
	eNOS	Slow-release eNOS substrate arginine (30) or blocking arginase (31, 32) to improve eNOS function and/or NO bioavailability in rodents and patients.
	FTO inhibition	Overcame glucose intolerance and insulin resistance and hypertension in mouse models of obesity (33).
	NOX inhibition	Inhibition of specific subunits ameliorated ROS-induced ED in rat model of obesity (34, 35).
	CD40L inhibition	Improved ROS-induced inflammation and ED in mouse models of obesity (36).
	NETs	Blocking formation or increased degradation in EC prevented ED in mouse model of obesity (37, 38).
	TRPV4 channels	Activity rescue improved ED (39), involving Ca2+-mediated vasoregulation (40), in mouse models of obesity.
	Soluble (pro)renin receptor inhibition	Soluble (pro)renin receptor induced ED and hypertension by activating AT1R leading to RAS hyperactivity in mouse models of obesity (41).
	AT (4)
	GRK2 inhibition	Reduced AT-macrophage infiltration and improved ED in mice (42).
	Anti-inflammation	Reduced AT-pro-inflammatory cytokine production by adipokine and leptin (43).
Dual-target	GLP1 agonist DPP4 inhibitors	Improved cardiovascular outcomes in patients of type 2 diabetes mellitus (44, 45) related to improved AT function (46).
	SGLT2 inhibitor	Cardioprotective (47) and beneficial for heart failure in patients (48).
	Anti-inflammation	Reduced AT-pro-inflammatory cytokine production and restored endothelial function by metformin (49), resveratrol (50), and methotrexate (51).
	Lifestyle intervention	Exercise improved EC function (52) or reversed ED (53). Calorie restriction improved vascular insulin sensitivity and reduced inflammation (54).