Table I.
CVD type | TSP-1 | TSP-2 | ||
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Effect | (Refs.) | Effect | (Refs.) | |
MI | TSP-1 polymorphism associated with MI | (56–58) | TSP-2 polymorphism promotes MI | (54) |
TSP-1 expression increases in patients with MI | (47) | Hypoxia induces TSP-2 expression in cardiomyocyte progenitor cells | (52) | |
TSP-1 protects the myocardium from fibrotic remodeling in MI | (50) | - | - | |
TSP-1 decreases following PCI associated with adverse cardiac events | (48) | - | - | |
Ischemia/reperfusion accelerate the induction of TSP-1 in rat MI model | (49) | - | - | |
Cardiac hypertrophy | TSP-1 protects pressure-overloaded myocardium | (60) | TSP-2 absence leads to age-associated dilated cardiomyopathy | (62) |
TSP-1 overexpression in the diabetic heart inhibits chamber dilation | (61) | TSP-2 absence enhances cardiomyocyte damage and matrix disruption in cardiomyopathy | (63) | |
- | - | TSP-2 prevents cardiac injury and dysfunction in viral myocarditis | (64) | |
- | - | TSP-2 expression marks an early-stage molecular program in hypertrophied hearts that may fail | (65) | |
Heart failure | TSP-1 expression decreases in failing hearts | (66,67) | Increased TSP-2 related to CHF-associated mortality and all-cause mortality among patients with CAD with CHF | (71) |
miRNA-18 and miRNA-19 modulate TSP-1 expression in age-associated HF | (69) | High serum TSP-2 levels correlate with poor prognosis in patients with HF | (72,73) | |
Oral anticoagulation therapy causes the decrease of TSP-1 in patients with HF | (70) | - | - | |
Valvular disease | Not available | TSP-2 increases in human fibrosclerotic and stenotic aortic valves | (75) | |
Cerebral and carotid artery disorder | Fluvastatin inhibits intimal hyperplasia after carotid artery ligation in WT but not Thbs1-null mice | (77) | TSP-2 small interfering RNA inhibits vascular response to the injury in rat carotid balloon angioplasty model | (82) |
TSP-1 expression increases in platelets from patients with CAD | (76) | TSP-2 deficiency leads to an impaired recovery following a stroke | (78,83) | |
TSP-1 increases following stroke, and TSP-1 deficiency leads | (78,83) | TSP-2 increases in ischemic brain and may lead to spontaneous to an impaired recovery following stroke angiogenesis | (79) | |
TSP-1 is highly expressed in the ischemic brain | (79) | Altered TSP-2 expression following spontaneous intracerebral hemorrhage is associated with angiogenesis | (81) | |
Altered TSP-1 expression following spontaneous intracerebral hemorrhage is related to angiogenesis | (81) | - | - | |
Atherosclerosis | TSP-1 increases in VSMC of human atherosclerotic lesions | (89) | TSP-2 was absent from the endothelium inside the atheromatous plaque | (97) |
TSP-1 increases in large arteries of diabetic animals and decreases in microvascular ECs | (89,93,94) | - | - | |
Proatherogenic flow initiates EC apoptosis and arterial stiffening via TSP-1 | (40,84) | - | - | |
TSP-1 deficiency inhibits atherogenic lesion formation in hyperglycemic ApoE(−/−) mice | (95) | - | - | |
TSP-1 deficiency promotes atherosclerotic plaque maturation in ApoE(−/−) mice | (85) | - | - | |
TSP-1 infiltrates into nascent atherosclerotic plaques and promotes atherogenesis | (86,88) | - | - | |
Injured arteries overexpress TSP-1 in hypercholesterolemic atherosclerotic rabbit | (87) | - | - | |
TSP-1 modulates SMC migration, promotes the development of atherosclerotic lesions | (90–92) | - | - | |
TSP-1 increases in hypoxic pulmonary and lead to pulmonary vascular remodeling | (96) | - | - | |
Angiogenesis | TSP-1 inhibits tumor angiogenesis | (22,100, 101) | TSP-2 inhibits the proliferation of microvascular ECs | (110, 111) |
TSP-1 overexpression in diabetes leads to an impaired angiogenesis | (102) | TSP-2 deficiency promotes angiogenesis | (112, 113) | |
TSP-1 may inhibit angiogenic responses in the ischemic retina | (103) | TSP-2 limits angiogenesis by decreasing gelatinolytic activity in situ | (114) | |
TSP-1 deficiency contributes to enhanced neovascularization in the eye | (104–108) | TSP-2 overexpression result in an inhibition of vascularization in rheumatoid arthritis | (115) | |
TSP-1 downregulation in EC enhances angiogenesis | (98,99) | Delayed TSP-2 expression in the wounds of aged mice impairs the rate of wound healing | (116) | |
- | - | Increased vessel density in TSP2−/− mice but not in TSP1−/− animals | (117) | |
Arterial restenosis | TSP-1 expression by VSMCs is an early response to injury | (118) | TSP-2 silencing of aortic SMCs improved cell attachment but did not affect cell migration or proliferation | (122) |
TSP-1 is not a major component of the ECM in human restenotic tissues | (121) | - | - | |
TSP-1 and β1 integrin interaction is related to platelet-stimulated SMC proliferation | (120) | - | - | |
TSP-1 may reverse the inward remodeling of resistance arteries from hypertension rat | (119) | - | - | |
Other CVDs | TSP-1 promotes pulmonary hypertension associated with hypoxia | (123) | TSP-2 deficient mice exhibit a bleeding diathesis despite normal blood coagulation | (127) |
TSP-1 deficiency accelerates aortic aneurysm progression | (124) | TSP-2 deficient mice exhibit an altered foreign body reaction characterized by increased vascularity | (128) | |
TSP-1 regulates the migration and adhesion of mononuclear cells and contributes to the vascular inflammation in AAA | (125) | TSP-2 elevates in acute Kawasaki disease | (130) | |
TSP-1-derived peptide RFYVVMWK may enhance the vascular engraftment during autologous proangiogenic cell therapy | (126) | TSP2-knockout leads to decreased fibrosis and increased EC density during cardiac cell transplantation | (131) | |
TSP-1 increases in the aorta and plasma of patients with acute aortic dissection | (23) |
CVD, cardiovascular disease; TSP, thrombospondin; MI, myocardial infarction; PCI, percutaneous coronary intervention; HF, heart failure; CHF, congestive heart failure; CAD, coronary artery disease; WT, wild-type; VSMC, vascular smooth muscle cell; EC, endothelial cell; ECM, extracellular matrix; AAA, abdominal aortic aneurysm; ApoE, apolipoprotein E.