Table 4.

Studies examining zinc transporters in cardiovascular disease

Zinc transporterExperimental modelProtocolQuantificationExpression changeReference
Protein expressionmRNA expression
ZIP1 CMs isolated from Sprague-Dawley rats (WT, male, 8 wk) In vivo chronic aldosterone/salt treatment, 4 wk  ✓ 
∼4.2-fold 
Kamalov et al., 2009  
 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.5 to ∼1.4 AU
↑ H/R
0.5 to ∼0.7 AU 
Bodiga et al., 2017  
ZIP2 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼1.3 AU
↓ H/R
1 to ∼0.8 AU (NS) 
Bodiga et al., 2017  
 Hearts from C57BL/6 mice (WT, male, 8–10 wk) In vivo I/R by left anterior descending coronary artery occlusion ✓ ✓ ↑ protein
∼150%
↑ mRNA
∼fourfold 
Du et al., 2019  
ZIP3 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼1.6 AU
↑ H/R
1 to ∼1.6 AU 
Bodiga et al., 2017  
ZIP6 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.8 to ∼1 AU (NS)
↓ H/R
0.8 to ∼0.7 AU (NS) 
Bodiga et al., 2017  
ZIP7 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼2 AU
↓ H/R
1 to ∼0.9 AU (NS) 
Bodiga et al., 2017  
ZIP7 Hearts from Wistar rats (WT, male, 2 mo) In vivo transverse aortic constriction ✓  
∼twofold 
Olgar et al., 2018b  
 H9C2 cell lysates In vitro DOX treatment ✓  
∼1.5-fold 
Tuncay et al., 2019  
 CMs isolated from C57BL/6 mice (WT, male, 8–10 wk) In vitro H/R ✓  
∼0.7 to ∼1.2 
Zhang et al., 2021  
 Hearts from Wistar rats (WT, male, 250–350 g) Ex vivo I/R ✓  
∼0.75 to ∼0.9 
Zhang et al., 2021  
 Hearts from C57BL/6 mice (WT, male, 8–10 wk) In vivo I/R by left anterior descending coronary artery occlusion ✓ ✓ ↑ protein
∼0.8 to ∼1
↑ mRNA from ∼1 to 2 
Zhang et al., 2021  
ZIP8 H9C2 cell lysates In vitro DOX treatment ✓  
∼0.4-fold 
Olgar et al., 2018a  
 Human heart failure tissue Patients with end-stage heart failure ✓  
∼0.5-fold 
Olgar et al., 2018a  
 Hearts from Wistar rats (WT, male, 2 mo) In vivo transverse aortic constriction ✓  
∼0.5-fold 
Olgar et al., 2018b  
ZIP9 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼2 AU
≈ H/R 
Bodiga et al., 2017  
ZIP10 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼1.5 AU
↑ H/R
1–∼1.2 (NS) 
Bodiga et al., 2017  
ZIP11 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼2 AU
≈ H/R 
Bodiga et al., 2017  
ZIP12 Human pulmonary artery smooth muscle cells In vitro hypoxia incubation  ✓ 
∼threefold 
Zhao et al., 2015  
ZIP13 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.5 to ∼2 AU
≈ H/R 
Bodiga et al., 2017  
ZIP13 Heart tissue from C57BL/6 mice (WT, male, 8–10 wk) In vivo left anterior descending coronary artery ligation ✓ ✓ ↓ protein
∼0.5-fold
↓ mRNA
∼0.6-fold 
Wang et al., 2021a  
 H9C2 cell lysates In vitro H/R ✓  
∼0.6-fold 
Wang et al., 2021b  
 Neonatal CMs isolated from newborn C57BL/6N mice In vitro DOX treatment  ✓ 
∼0.75 to ∼0.1 
Hara et al., 2022  
 Heart tissue from C57BL/6N mice In vivo intraperitoneal DOX injection  ✓ 
∼1 to ∼0.6 
Hara et al., 2022  
ZIP14 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.5 to ∼2 AU
≈ H/R 
Bodiga et al., 2017  
 H9C2 cell lysates In vitro DOX treatment ✓  
∼1.5-fold 
Olgar et al., 2018a  
 Human heart failure tissue Patients with end-stage heart failure ✓  
∼twofold 
Olgar et al., 2018a  
 Heart tissue from Wistar rats (WT, male, 2 mo) In vivo transverse aortic constriction ✓  
∼2.5-fold 
Olgar et al., 2018b  
ZnT1 Cultures CMs from rats (1–2 d old) In vitro rapid pacing ✓  
214.4% 
Beharier et al., 2007  
 Heart homogenates from Sprague-Dawley rats (WT, male, 250–350 g) In vivo rapid atrial pacing ✓  
148% 
Beharier et al., 2007  
 Human cardiac tissue Cardiac tissue obtained from control and atrial fibrillation patients ✓  
0.73–1.88 
Etzion et al., 2008  
 CMs from Sprague-Dawley rats (WT, male, 8 wk) In vivo chronic aldosterone/salt treatment, 4 wk  ✓ 
∼twofold 
Kamalov et al., 2009  
 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼2 AU

1 to ∼1.2 AU (NS) 
Bodiga et al., 2017  
ZnT2 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.5 to ∼0.6 AU (NS)
↑ H/R
0.4 to ∼1.4 AU 
Bodiga et al., 2017  
ZnT5 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ≈ hypoxia
↑ H/R
0.8 to 1.2 AU 
Bodiga et al., 2017  
ZnT7 Hearts from Wistar rats (WT, male, 2 mo) In vivo transverse aortic constriction ✓  
∼0.6-fold 
Olgar et al., 2018b  
 H9C2 cell lysates In vitro DOX treatment ✓  
∼0.5-fold 
Tuncay et al., 2019  
ZnT8 H9C2 cell lysates In vitro DOX treatment ✓  
∼1.6-fold 
Olgar et al., 2018a  
 Human heart failure tissue Patients with end-stage heart failure ✓  
∼twofold 
Olgar et al., 2018a  
 Hearts from Wistar rats (WT, male, 2 mo) In vivo transverse aortic constriction ✓  
∼1.5-fold 
Olgar et al., 2018b  
ZnT9 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.8 to ∼1 AU (NS)
↑ H/R
0.8 to ∼1.1 AU (NS) 
Bodiga et al., 2017  
Zinc transporterExperimental modelProtocolQuantificationExpression changeReference
Protein expressionmRNA expression
ZIP1 CMs isolated from Sprague-Dawley rats (WT, male, 8 wk) In vivo chronic aldosterone/salt treatment, 4 wk  ✓ 
∼4.2-fold 
Kamalov et al., 2009  
 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.5 to ∼1.4 AU
↑ H/R
0.5 to ∼0.7 AU 
Bodiga et al., 2017  
ZIP2 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼1.3 AU
↓ H/R
1 to ∼0.8 AU (NS) 
Bodiga et al., 2017  
 Hearts from C57BL/6 mice (WT, male, 8–10 wk) In vivo I/R by left anterior descending coronary artery occlusion ✓ ✓ ↑ protein
∼150%
↑ mRNA
∼fourfold 
Du et al., 2019  
ZIP3 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼1.6 AU
↑ H/R
1 to ∼1.6 AU 
Bodiga et al., 2017  
ZIP6 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.8 to ∼1 AU (NS)
↓ H/R
0.8 to ∼0.7 AU (NS) 
Bodiga et al., 2017  
ZIP7 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼2 AU
↓ H/R
1 to ∼0.9 AU (NS) 
Bodiga et al., 2017  
ZIP7 Hearts from Wistar rats (WT, male, 2 mo) In vivo transverse aortic constriction ✓  
∼twofold 
Olgar et al., 2018b  
 H9C2 cell lysates In vitro DOX treatment ✓  
∼1.5-fold 
Tuncay et al., 2019  
 CMs isolated from C57BL/6 mice (WT, male, 8–10 wk) In vitro H/R ✓  
∼0.7 to ∼1.2 
Zhang et al., 2021  
 Hearts from Wistar rats (WT, male, 250–350 g) Ex vivo I/R ✓  
∼0.75 to ∼0.9 
Zhang et al., 2021  
 Hearts from C57BL/6 mice (WT, male, 8–10 wk) In vivo I/R by left anterior descending coronary artery occlusion ✓ ✓ ↑ protein
∼0.8 to ∼1
↑ mRNA from ∼1 to 2 
Zhang et al., 2021  
ZIP8 H9C2 cell lysates In vitro DOX treatment ✓  
∼0.4-fold 
Olgar et al., 2018a  
 Human heart failure tissue Patients with end-stage heart failure ✓  
∼0.5-fold 
Olgar et al., 2018a  
 Hearts from Wistar rats (WT, male, 2 mo) In vivo transverse aortic constriction ✓  
∼0.5-fold 
Olgar et al., 2018b  
ZIP9 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼2 AU
≈ H/R 
Bodiga et al., 2017  
ZIP10 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼1.5 AU
↑ H/R
1–∼1.2 (NS) 
Bodiga et al., 2017  
ZIP11 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼2 AU
≈ H/R 
Bodiga et al., 2017  
ZIP12 Human pulmonary artery smooth muscle cells In vitro hypoxia incubation  ✓ 
∼threefold 
Zhao et al., 2015  
ZIP13 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.5 to ∼2 AU
≈ H/R 
Bodiga et al., 2017  
ZIP13 Heart tissue from C57BL/6 mice (WT, male, 8–10 wk) In vivo left anterior descending coronary artery ligation ✓ ✓ ↓ protein
∼0.5-fold
↓ mRNA
∼0.6-fold 
Wang et al., 2021a  
 H9C2 cell lysates In vitro H/R ✓  
∼0.6-fold 
Wang et al., 2021b  
 Neonatal CMs isolated from newborn C57BL/6N mice In vitro DOX treatment  ✓ 
∼0.75 to ∼0.1 
Hara et al., 2022  
 Heart tissue from C57BL/6N mice In vivo intraperitoneal DOX injection  ✓ 
∼1 to ∼0.6 
Hara et al., 2022  
ZIP14 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.5 to ∼2 AU
≈ H/R 
Bodiga et al., 2017  
 H9C2 cell lysates In vitro DOX treatment ✓  
∼1.5-fold 
Olgar et al., 2018a  
 Human heart failure tissue Patients with end-stage heart failure ✓  
∼twofold 
Olgar et al., 2018a  
 Heart tissue from Wistar rats (WT, male, 2 mo) In vivo transverse aortic constriction ✓  
∼2.5-fold 
Olgar et al., 2018b  
ZnT1 Cultures CMs from rats (1–2 d old) In vitro rapid pacing ✓  
214.4% 
Beharier et al., 2007  
 Heart homogenates from Sprague-Dawley rats (WT, male, 250–350 g) In vivo rapid atrial pacing ✓  
148% 
Beharier et al., 2007  
 Human cardiac tissue Cardiac tissue obtained from control and atrial fibrillation patients ✓  
0.73–1.88 
Etzion et al., 2008  
 CMs from Sprague-Dawley rats (WT, male, 8 wk) In vivo chronic aldosterone/salt treatment, 4 wk  ✓ 
∼twofold 
Kamalov et al., 2009  
 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
1 to ∼2 AU

1 to ∼1.2 AU (NS) 
Bodiga et al., 2017  
ZnT2 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.5 to ∼0.6 AU (NS)
↑ H/R
0.4 to ∼1.4 AU 
Bodiga et al., 2017  
ZnT5 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ≈ hypoxia
↑ H/R
0.8 to 1.2 AU 
Bodiga et al., 2017  
ZnT7 Hearts from Wistar rats (WT, male, 2 mo) In vivo transverse aortic constriction ✓  
∼0.6-fold 
Olgar et al., 2018b  
 H9C2 cell lysates In vitro DOX treatment ✓  
∼0.5-fold 
Tuncay et al., 2019  
ZnT8 H9C2 cell lysates In vitro DOX treatment ✓  
∼1.6-fold 
Olgar et al., 2018a  
 Human heart failure tissue Patients with end-stage heart failure ✓  
∼twofold 
Olgar et al., 2018a  
 Hearts from Wistar rats (WT, male, 2 mo) In vivo transverse aortic constriction ✓  
∼1.5-fold 
Olgar et al., 2018b  
ZnT9 CMs isolated from Wistar Kyoto rats In vitro H/R ✓  ↑ hypoxia
0.8 to ∼1 AU (NS)
↑ H/R
0.8 to ∼1.1 AU (NS) 
Bodiga et al., 2017  

Changes observed in ZIPs and ZnTs in conditions of cardiovascular disease including experimental model, expression change, and study. All expression changes are significant except where NS (not significant) is specified. CMs, cardiomyocytes; DOX, doxorubicin; H/R, hypoxia/reoxygenation. ↑ denotes increased expression; ↓ illustrates a decrease in expression; ≈ shows no change.

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