References

Animal models or cell types

Statins studied

Effects of statins

Cx expression and gap junction

Improvement of pathological changes

Part 1: Modulation of Cxs/gap junctions by statins against atherosclerosis and neointimal hyperplasia

[25]

rabbits fed with high-cholesterol diet

lovastatin, fluvastatin

expressions of Cx43 and Cx 40 in lesions reduced, volume and size of gap junctions between SMCs reduced

neointima decreased in atherosclerotic lesions

[29]

LDLR^−/− mice fed with cholesterol-rich diet

pravastatin

Cx43 expression reduced in lesions

improvement of plaque morphology and stability

cultured SMCs isolated from human saphenous veins

simvastatin

Cx43 expression reduced, reduced transfer of gap junction-permeable dye

ND

[32]

rabbits fed with high-cholesterol diet

vytorin (simvastatin/ ezetimebe)

Cx43 expression reduced in aortic walls

neointimal hyperplasia and inflammatory cell infiltration reduced in lesions

cultured rat aortic SMCs, stimulated with or without TNF-α/IL-18

simvastatin

Cx43 expression reduced (constitutive level as well as increased expression induced by TNF-α/IL-18)

over-proliferation of SMCs suppressed

[27]

rabbits, arteries subjected to balloon injury

lovastatin, fluvastatin

expressions of Cx43 and Cx40 reduced in neointimal SMCs, volume and size of gap junctions reduced

neointima decreased

[33]

ex vivo cultured human saphenous veins

fluvastatin

expression of Cx43 reduced in neointimal SMCs

neointima decreased

[34]

cultured rat aortic SMCs

lovastatin

GJIC inhibited between SMCs

migration of SMCs inhibited

[35]

cultured SMCs isolated from human saphenous veins

atorvastatin controlled release from hydrogel

expression of Cx43 reduced

proliferation and migration of SMCs inhibited

[37]

rat diabetes induced by STZ injection

simvastatin

reversed the down-regulation of Cx 43 in aortic walls of diabetic mice

ND

[39]

hereditary HTG rats

atorvastatin

Cx43 expression reduced in aorta, distribution of Cx43 modified between endothelium and media

integrity of endothelium improved

[40]

cultured HUVEC

fluvastatin, lovastatin, pravastatin, simvastatin

statins reduced Cx43 expression when treated alone, but could reverse the down-regulating effect of nicotine on Cx43

ND

[41]

mice hyperlipidemia induced by cholesterol-rich diet

simvastatin

reversed the reduction of Cx37 and gap junctions in aortic endothelium

ND

[42]

STZ induced diabetes in ApoE-deficient mice

simvastatin

exacerbated the reduction of Cx37 and Cx 40 in aortic endothelium

-

Part 2: Modulation of Cxs/gap junctions by statins against arrhythmia and myocardial injury/hypertrophy

[48]

hereditary HTG rats

atorvastatin

Cx43 expression increased, phosphorylation normalized; gap junction remodeling suppressed, integrity improved in ventricles

threshold for electric-induced VF increased

[49]

rat acute MI induced by coronary artery ligation

pravastatin

Cx43 expression increased, gap junction remodeling suppressed

incidence of VT/VF decreased

[50] [51]

mice viral myocarditis induced by CVB3

atorvastatin, pravastatin

restored the reduction of Cx43 and Cx 45 in hearts, suppressed gap junction remodeling

myocardial inflammatory cell infiltration and necrosis decreased, animal survival rate increased