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Table 4 Summary of the effects of SGLT-2 inhibitors on cardiac inflammation in animal models

From: Potential mechanisms responsible for cardioprotective effects of sodium–glucose co-transporter 2 inhibitors

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]
  1. 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