Susceptibility of Rat Steatotic Liver to Ischemia-Reperfusion Is Treatable With Liver-Selective Matrix Metalloproteinase Inhibition.

ABSTRACT:

Background and aims

This study examined whether enhanced susceptibility of steatotic liver to ischemia-reperfusion (I/R) injury is due to impaired recruitment of bone marrow (BM) progenitors of liver sinusoidal endothelial cells (LSECs, also called sinusoidal endothelial cell progenitor cells [sprocs]) with diminished repair of injured LSECs and whether restoring signaling to recruit BM sprocs reduces I/R injury.

Approach and results

Hepatic vessels were clamped for 1 hour in rats fed a high-fat, high-fructose (HFHF) diet for 5, 10, or 15 weeks. Matrix metalloproteinase 9 (MMP-9) antisense oligonucleotides (ASO) or an MMP inhibitor were used to induce liver-selective MMP-9 inhibition. HFHF rats had mild, moderate, and severe steatosis, respectively, at 5, 10, and 15 weeks. I

SUBMITTER: Wang X 

PROVIDER: S-EPMC7523533 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature