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. 2019 Apr 11;8(4):495. doi: 10.3390/jcm8040495

Table 1.

Role of lymphatics in mRCT and immune cells trafficking in the arterial wall.

Reference Murine Model Intervention/Treatment Site of Lymphatic Function Assessment Outcome
Martel et al. [13] WT C57BL/6 Disruption of tail lymphatics and injection of [3H]-cholesterol–loaded macrophages into the tail distal to lymphatic disruption Tail Reduced [3H]-Cholesterol levels in plasma, liver and feces of mice with lymphatic disruption
Martel et al. [13] Chy mice Injection of [3H]-cholesterol–loaded macrophages into the footpads Footpad skin Decreased RCT in Chy mice compared with control mice
Martel et al. [13] ApoE−/−

Regression model
Transplantation of [2H]6−labeled cholesterol-loaded aorta to ApoE−/− mice treated with a VEGFR3 blocking antibody

ApoE adenoviral vector
Aorta Reduced RCT in VEGFR3 blocking antibody-treated mice
Vuorio et al. [16] Chy×LDLR−/−/ApoB100/100

sVEGFR3×LDLR−/−/ApoB100/100
Normal chow diet or Western diet Elevated plasma cholesterol levels in Chy mice compared with control mice on chow as well as Western diet

No change in plasma cholesterol levels among sVEGFR3×LDLR−/−/ApoB100/100 mice and respective controls

Accelerated atherosclerosis in young and middle-aged sVEGFR3 mice compared with control mice after 6 weeks of Western diet
Lim et al. [12] ApoE−/− Regular chow diet and VEGF-C treatment

Surgical disruption of afferent lymphatic vessels
Peritoneal cavity and skin Improved lymphatic transport and reduced peripheral lipid accumulation in VEGF-C-treated mice.

Decreased RCT in mice with excised lymphatic vessels
Milasan et al. [14] Pcsk9−/−

LDLR−/−; hApoB100/100
Regular chow diet and VEGF-C152S treatment Footpad and back skin Improved collecting lymphatic vessel function in Pcsk9−/− mice.

VEGF-C-treated LDLR−/−; hApoB100/100 mice
Taher et al. [156] ApoE−/− Western diet Decreased lymphatic vessel density in aged and Western diet-fed mice due to increased expression of sVEGFR2 in aortic tissue
Milasan et al. [157] LDLR−/− Western diet and apoA-I treatment Footpad and back skin Enhanced lymphatic transport, improved LV permeability and reduced atherosclerotic lesion formation in apoA-I-treated mice
Rademakers et al. [15] ApoE−/− Western diet

Semi-constrictive collars on carotid artery

Dissection of plaque draining lymph node and lymphatic vessel
Aggravated atherosclerotic lesion formation

Accumulation of CD3+ T cells in the carotid artery
Rademakers et al. [15] ApoE−/− Western diet

AAV-hVEGFR3 treatment
Accumulation of CD3+ T cells in the intima and adventitia
Milasan et al. [62] LDLR−/−Regression model VEGF-C152S pretreatment

Western diet for 8 weeks and one group switched to regular chow diet after 8 weeks
Footpad and back skin VEGF-C pretreatment improved lymphatic transport and attenuated plaque formation in mice sacrificed after Western diet period