Table 3.
The interaction between tregs and parenchymal cells in HF .
| Cell Type | Parenchymal Cells in HF | Interaction Between Tregs and Parenchymal cells |
|---|---|---|
| Cardiomyocyte | Cardiomyocyte is the main cell type in the heart. It participates in heart contraction and produces pro-inflammatory factors under stress conditions. | ①Tregs reduced pro-inflammatory factor production of hypoxic cardiomyocytes in vitro (22). ②Tregs reduced the apoptosis of hypoxic cardiomyocytes and ameliorated cardiac function in MI mice (22, 26). ③Tregs promoted cardiomyocyte proliferation directly (116, 117). |
| Fibroblast | Fibroblast is the main cell type in the heart. During heart damage, fibroblasts are activated and participate in tissue repair and adverse ventricular remodeling. ①Fibroblasts in the heart were heterogeneous populations and constituted multiple subsets. FSP1-expressing fibroblasts participated in promoting angiogenesis and played a protective role in MI (118, 120). ②Excessive activation of fibroblasts and diminished apoptosis of myofibroblasts participated in poor repair after heart injury (119). |
①Tregs accumulated in MI heart produced SPARC, which reduced heart rupture by increasing the production of collagen III in fibroblasts. In vitro, coculture of fibroblasts with SPARC-overexpressing Tregs had the same effect (20). ②In vitro, Tregs reduced the expression of α-SMA and MMP3 in fibroblasts and attenuated the contraction of fibroblast-populated collagen pads (52). |
| Endothelial cell (EC) |
Cardiac ECs participate in the regulation of vascular integrity and have dual effects in coagulation and anti-coagulation. ①Hypoxia promoted activated ECs to form vessels in ischemic and hypertrophic hearts (121). |
①Elimination of Tregs decreased the production of vascular protective related proteins in ECs and worsened pulmonary hypertension. In coculture of human heart microvascular ECs with Tregs, these proteins increased (122). ②Tregs inhibited the activation of ECs induced by ox-LDL, LPS, fine particles, and vasoactive substances (123–125). ③Adoptive transfer of Tregs induced an increase in small capillaries in MI (97). ④Tregs became Th1-like cells with an antiangiogenic effect in HF. This effect was related to the expression of TNFR1 on Tregs (31). ⑤Tregs protected the integrity of vascular endothelium and reduced the leukocyte transcellular migration (127). ⑥In coculture of Tregs with HUVECs, the suppressive function of Tregs on effector T cells increased (129). ⑦HLA-DR+ ECs promoted Treg proliferation through the surface marker CD54 (130). |
FSP, fibroblast specific protein; MI, myocardial infarction; EC, endothelial cells; SPARC, secreted protein acidic and rich in cysteine; SMA, smooth muscle actin; MMP, matrix metalloproteinase; ox-LDL, Oxidation Low Lipoprotein; LPS, lipopolysaccharide; HF, heart failure; TNFR, tumor necrosis factor receptor; HUVEC, human umbilical vein endothelial cell; HLA, human leukocyte antigen.