Table 4.
Summary of the effects of SGLT-2 inhibitors on cardiac inflammation in animal models
| Animal species | Model | Drug/dose/route | Major findings | Interpretation | References |
|---|---|---|---|---|---|
| SHR/NDmcr-cp (+/+) rats | Prediabetes/metabolic syndrome | 0.03% empagliflozin/diet/10 weeks | ↓ Cardiac interstitial macrophage infiltration | Empagliflozin attenuated cardiac macrophage infiltration in genetic prediabetic metabolic syndrome rats | [57] |
| db/db mice | Diabetes/obesity (diastolic dysfunction and LVH) | 0.03% empagliflozin/diet/10 weeks | ↓ Cardiac macrophage infiltration | Empagliflozin attenuated cardiac macrophage infiltration in db/db mice | [58] |
| BTBR ob/ob mice | T2DM | Dapagliflozin (1 mg/kg/days)/PO/8 weeks | ↓ NALP-3, ASC, caspase-1, IL-1β, IL-6 and TNFα expressions | Dapagliflozin attenuated NLRP3 inflammasome and inflammatory markers in BTBR ob/ob mice | [63] |
| BTBR ob/ob mice | In vitro cardiofibroblast culture | Dapagliflozin (0.1–0.5 μM)/media/16 h | ↓ NALP-3, ASC, caspase-1 and IL-1β expressions in dose dependent manner |
Dapagliflozin attenuated NLRP3 inflammasome and inflammatory markers in cardiofibroblasts of BTBR ob/ob mice These effects are independent from SGLT-2 and glucose reducing effects of dapagliflozin |
[63] |
| Wistar rats | MI by LAD ligation in rats | Dapagliflozin (0.1 mg/kg/days)/PO/Start after 1-day infarction for 2 days |
↑ M2/M1 phenotype macrophage ratio and IL-10 mRNA level ↓ IL-1β and IL-6 mRNA levels |
Dapagliflozin promoted macrophages toward anti-inflammatory phenotype, increased anti-inflammatory cytokine and attenuated inflammatory cytokines in rats with acute stage of MI | [65] |
| cmlc2::GFP zebrafish embryos | Aristolochic acid induced heart failure | Empagliflozin (0.1, 10 μM)/media/3 days | ↓ Cox-2, IL-1β expressions | Empagliflozin attenuated pro-inflammatory genes in heart failure zebrafish model | [66] |
SGLT-2 sodium–glucose co-transporter 2, LVH left ventricular hypertrophy, T2DM type 2 diabetic mellitus, NALP-3 NACHT, LRR and PYD domains-containing protein 3, ASC apoptosis-associated speck-like protein containing a caspase recruitment domain, IL interleukin, TNFα tumor necrosis factor α, NLRP3 nucleotide-binding oligomerization domain-like receptor 3, MI myocardial infarction, LAD left anterior descending artery, Cox-2 cyclooxygenase-2