Kidney Week

Abstract: SA-OR095

Mitoprotection Preserves the Renal Microvasculature in Porcine Metabolic Syndrome

Session Information

• Vascular Biology and Dysfunction
  November 04, 2017 | Location: Room 394, Morial Convention Center
  Abstract Time: 05:18 PM - 05:30 PM

Category: Hypertension

• 1103 Vascular Biology and Dysfunction

Authors

• Eirin, Alfonso, Mayo Clinic, Rochester, Minnesota, United States

Alfonso Eirin, MD



• Hedayat, Ahmad Fahim, Mayo Clinic, Rochester, Minnesota, United States

Ahmad Fahim Hedayat,

• Ferguson, Christopher M., Mayo Clinic, Rochester, Minnesota, United States

Christopher M. Ferguson,

• Jordan, Kyra L., Mayo Clinic, Rochester, Minnesota, United States

Kyra L. Jordan,

• Textor, Stephen C., Mayo Clinic, Rochester, Minnesota, United States

Stephen C. Textor,

• Lerman, Amir, Mayo Clinic, Rochester, Minnesota, United States

Amir Lerman,

• Lerman, Lilach O., Mayo Clinic, Rochester, Minnesota, United States

Lilach O. Lerman,

Background

The metabolic syndrome (MetS) induces intra-renal microvascular disease, which may involve mitochondrial injury. The mitochondrial cardiolipin-targeting peptide elamipretide (ELAM) improves the microcirculation in post-stenotic kidneys, but its potential for attenuating MetS-induced microvascular dysfunction is unknown. We hypothesized that chronic treatment with ELAM would decrease vascular remodeling and dysfunction in swine MetS.

Methods

Pigs were studied after 16 weeks of diet-induced MetS, MetS after 4 weeks of ELAM treatment (0.1mg/kg SC q.d), and Lean controls (n=6 each). Vascular endothelial cell (EC) mitochondrial density (electron microscopy) and cardiolipin content (10N-nonyl acridine orange staining) were assessed in situ. The density of peritubular capillaries (PTC, H&E staining) and renal microvessels (20-500μm, 3D micro-CT), and the function of renal artery segments (organ bath, endothelial nitric oxide (eNOS) expression) were characterized.

Results

MetS pigs developed obesity, hypertension, hyperlipidemia, and insulin resistance. Mitochondrial density and cardiolipin content in EC were diminished in MetS, but improved in ELAM-treated pigs. Furthermore, ELAM improved PTC and microvascular density, and restored eNOS expression and endothelial-dependent relaxation of renal artery segments.

Conclusion

MetS-induced mitochondrial alterations might contribute to renal PTC and microvascular loss, and impair renal artery endothelial function in pigs. These observations suggest a potential role for mitoprotection in preserving the renal microvasculature in MetS.

Funding

• NIDDK Support – Stealth BioTherapeutics, Inc.