Affordable Access

Access to the full text

Estrogen modulates the differential expression of cardiac myocyte chymase isoforms and diastolic function

Authors
  • Wang, Hao1, 2
  • Sun, Xuming1
  • Ahmad, Sarfaraz3
  • Su, Jing4
  • Ferrario, Carlos Maria3, 5, 6
  • Groban, Leanne1, 2
  • 1 Wake Forest School of Medicine, Department of Anesthesiology, Medical Center Blvd, Winston-Salem, NC, 27157, USA , Winston-Salem (United States)
  • 2 Wake Forest School of Medicine, Department of Internal Medicine-Molecular Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA , Winston-Salem (United States)
  • 3 Wake Forest School of Medicine, Department of Surgery, Medical Center Blvd, Winston-Salem, NC, 27157, USA , Winston-Salem (United States)
  • 4 Wake Forest School of Medicine, Division of Public Health Sciences, Department of Biostatistical Sciences, Medical Center Blvd, Winston-Salem, NC, 27157, USA , Winston-Salem (United States)
  • 5 Wake Forest School of Medicine, Department of Physiology and Pharmacology, Medical Center Blvd, Winston-Salem, NC, 27157, USA , Winston-Salem (United States)
  • 6 Wake Forest University School of Medicine, Division of Public Health Sciences, Department of Social Sciences and Health Policy, Medical Center Blvd, Winston-Salem, NC, 27157, USA , Winston-Salem (United States)
Type
Published Article
Journal
Molecular and Cellular Biochemistry
Publisher
Springer-Verlag
Publication Date
Feb 02, 2019
Volume
456
Issue
1-2
Pages
85–93
Identifiers
DOI: 10.1007/s11010-018-03492-6
Source
Springer Nature
Keywords
License
Yellow

Abstract

Chymases, a family of serine proteases with chymotryptic activity, play a significant role in cardiac angiotensin II (Ang II) formation from its substrate Ang-(1-12) in both human and rodent models. No studies, to date, have assessed the differences in enzymatic activity among these isoforms in Ang II formation, particularly in the cardiomyocyte (CM). Using PCR and DNA sequencing, we demonstrated that MCP-1, MCP-2, MCP-4, and MCP-5 mRNAs are expressed in the CM of both spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY). While rMCP-1 and rMCP-5 gene transcripts were higher than that of other isoforms in both rat strains, WKY CM exhibits higher levels of rMCP-1 and rMCP-5 mRNAs compared to the SHR CM. Ovariectomy (OVX) increased the expression of rMCP-1 and rMCP-5 mRNAs in WKY. In SHR, OVX was associated with a blunted increase in rMCP-1 mRNA compared to OVX normotensive WKY. Chymase activity, measured as Ang II formation from Ang-(1-12), significantly correlated with rMCP-1 and rMCP-5 mRNA expression in both rat strains. Both rMCP-1 and rMCP-5 mRNA expressions were positively correlated with progressive diastolic dysfunction (increasing the ratio of early mitral inflow velocity-to-early mitral annular velocity, E/e′) and expanding chamber dimensions or increasing left ventricular internal diameter end diastole. These data show rMCP-1 and rMCP-5 as the Ang II forming chymase isoforms participating in the loss of normal cardiac function due to OVX in rodents.

Report this publication

Statistics

Seen <100 times