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

Lahnwong, Charshawn; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

doi:10.1186/s12933-018-0745-5

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]

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

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