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Sabe et al. Vessel Plus 2024;8:2 https://dx.doi.org/10.20517/2574-1209.2023.95 Page 7 of 12

Figure 3. Sitagliptin increases coronary microvessel collateralization in chronically ischemic myocardium compared to canagliflozin.
Capillary and arteriolar density in swine treated with canagliflozin (CANA, eight animals), sitagliptin (SIT, five animals), and vehicle
containing no medication (CON, seven animals) shown on box and whisker plots.

Figure 4. Immunoblot results in chronically ischemic myocardium with canagliflozin and sitagliptin. Data shown from immunoblot
experiments in chronically ischemic myocardium in swine treated with canagliflozin (CANA, n = 8), sitagliptin (SIT, n = 5), and vehicle
with no drug (CON, n = 8). *signifies a P value of less than 0.05.

SGLT2i have shown significant promise as a cardioprotective agent in basic and clinical studies. They have
been shown to reduce the risk of cardiovascular death, stroke, and non-fatal myocardial infarction,
irrespective of the presence of diabetes [3-5,23-28] . These positive trials prompted the recommendation of these
agents in patients with heart failure even in the absence of diabetes . Animal studies investigating
[17]
mechanistic explanations for these benefits have shown that SGLT2i reduce infarct size, improve cardiac
function, attenuate oxidative stress, and improve endothelium-dependent vasodilation . Another
[7-9]
commonly used class of antihyperglycemic agents, DPP4i, have shown cardioprotective effects in small and
large animal models, including improved cardiac function, reduced apoptosis and oxidative stress,
attenuated fibrosis, and improved endothelial proliferation [10-13] . We have previously investigated the effects
of canagliflozin and sitagliptin on cardiac function and microvascular collateralization and perfusion in our
large animal model of chronic myocardial ischemia, and we previously discussed these effects in relation to
prior studies. However, to our knowledge, the present study is the first to investigate the comparative effects