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. 2020 Feb 20;45(5):1275–1293. doi: 10.3892/ijmm.2020.4507

Table I.

Role of TSP-1 and TSP-2 in various CVDs.

CVD type TSP-1 TSP-2


Effect (Refs.) Effect (Refs.)
MI TSP-1 polymorphism associated with MI (5658) 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 (9092) - -
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 (104108) 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.