Altered Expression of Intestinal Duodenal Cytochrome B and Divalent Metal Transporter 1 Might Be Associated With Cardio-Renal Anemia Syndrome

Heart Vessels. 2017 Nov;32(11):1410-1414. doi: 10.1007/s00380-017-1013-4. Epub 2017 Jul 1.

Abstract

The interaction among heart failure (HF), chronic kidney disease (CKD), and anemia is called cardio-renal anemia syndrome. The mechanism of anemia in cardio-renal anemia syndrome is complex and remains completely unknown. We have previously reported that impaired intestinal iron transporters may contribute to the mechanism of anemia in HF using in vivo HF model rats. In this study, we assessed intestinal iron transporters in CKD model rats to investigate the association of intestinal iron transporters in the mechanism of cardio-renal anemia syndrome. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. Sham-operated rats served as a control. After 24-week surgery, CKD rats exhibited normocytic normochromic anemia and normal serum erythropoietin levels despite of anemia. Serum iron levels were decreased in CKD rats compared with the controls. Of interest, intestinal expression of critical iron importers, such as duodenal cytochrome b (Dcyt-b) and divalent metal transporter 1 (DMT-1), was decreased in CKD rats compared with the controls. On the other hand, intestinal expression of ferroportin, an intestinal iron exporter, was not different in the control and CKD groups. Moreover, hepatic expression of hepcidin, a regulator of iron homeostasis, did not differ between the control and CKD groups. These results suggest that impaired intestinal expression of Dcyt-b and DMT-1 might be associated with the reduction of an iron uptake in CKD. Taken together, impaired these intestinal iron transporters may become a novel therapeutic target for cardio-renal anemia syndrome.

Keywords: Cardio-renal anemia syndrome; Divalent metal transporter 1; Duodenal cytochrome b; Iron.

MeSH terms

  • Anemia / genetics*
  • Anemia / metabolism
  • Animals
  • Cardio-Renal Syndrome / genetics*
  • Cardio-Renal Syndrome / metabolism
  • Cation Transport Proteins / biosynthesis
  • Cation Transport Proteins / genetics*
  • Cytochromes b / biosynthesis
  • Cytochromes b / genetics*
  • Disease Models, Animal
  • Duodenum / metabolism*
  • Gene Expression Regulation*
  • Male
  • RNA / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Cation Transport Proteins
  • solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
  • RNA
  • Cytochromes b