Table 3.

Involvement of large middle molecules with cardiovascular disease

Middle Molecule	Association	Possible Mechanisms
IL-18	Cardiovascular mortality; aortic pulse wave velocity; unstable coronary plaque; coronary and thoracic aortic calcification	Promotion of atherosclerotic plaque instability, induction of IFN-γ, promotion of collagen and lipid deposition
IL-6	Left ventricular hypertrophy, systolic dysfunction; cardiovascular mortality	Coordination of local inflammatory cell influx and lymphocyte proliferation; promotion of coagulation
IL-1β	Left ventricular hypertrophy	Promotion of local inflammatory response within plaque
TNF-α	Left ventricular hypertrophy	Promotion of cardiac inflammatory response to stress
Pentraxin-3	Unstable coronary plaque	Infiltration of neutrophils into atherosclerotic plaque, prothrombotic effects, impairment of NO production
β-Trace protein	Atherosclerotic plaque; cardiovascular mortality	Possible functions acting against platelet aggregation via catalyzation of PGD2 production
Prolactin	Cardiovascular mortality	Proliferation of vascular smooth muscle cells, promotion of vasoconstriction
AGEs	Cardiovascular mortality	Deposition within vessel wall; induction of oxidative stress, inflammation, and endothelial dysfunction
Visfatin	Unstable atherosclerotic plaque	Induction of inflammatory macrophages within atherosclerotic plaque
Adiponectin	Atherosclerotic plaque	Expression of adhesion molecules; foam cell formation
Leptin	Atherosclerotic plaque	Expression of adhesion molecules; production of MCP-1, IL-6, and TNF-α
FGF-2	Cardiac hypertrophy	Induction of cardiomyocyte hypertrophic response
FGF-23	Cardiac hypertrophy	Induction of cardiomyocyte hypertrophic response

NO, nitric oxide; AGE, advanced glycosylation end products FGF, fibroblast growth factor.