Korean J Pediatr.  2019 Mar;62(3):95-101. 10.3345/kjp.2018.06856.

Changes of Bax, Bcl-2, CCR-2, MCP-1, and TGF-β1 genes in the left ventricle of spontaneously hypertensive rat after losartan treatment

• Lee H
• Kim KC
• Hong YM

• KMID: 2447196
• DOI: http://doi.org/10.3345/kjp.2018.06856

Abstract

PURPOSE
Increased apoptosis was recently found in the hypertrophied left ventricle of spontaneously hypertensive rats (SHRs). Although the available evidence suggests that apoptosis can be induced in cardiac cells by various insults including pressure overload, cardiac apoptosis appears to result from an exaggerated local production of angiotensin in adult SHRs. Altered expressions of Bcl associated X (Bax), Bcl-2, chemokine receptor (CCR)-2, monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-β1, phosphorylated extracellular signal-regulated kinases (PERK), and connexin 43 proteins, and kallikrein mRNA were investigated to explore the effects of losartan on the SHR model.
METHODS
Twelve-week-old male rats were grouped as follows: control (C), SHR (hypertension: H), and losartan (L; SHRs were treated with losartan [10 mg/kg/day] for 5 weeks). Western blot and reverse transcription polymerase chain reaction assays were performed.
RESULTS
Expression of Bax, CCR-2, MCP-1, TGF-β1, PERK, and connexin 43 proteins, and kallikrein mRNA was significantly increased in the H group compared to that in the C group at weeks 3 and 5. Expression of Bax, CCR-2, MCP-1, TGF-β1, and connexin 43 proteins and kallikrein mRNA was significantly decreased after losartan treatment at week 5. PERK protein expression was significantly decreased after losartan treatment at weeks 3 and 5. Bcl-2 protein expression was significantly decreased in the H group compared to that in the C group at weeks 3 and 5.
CONCLUSION
Losartan treatment reduced expression of Bax, CCR-2, MCP-1, TGF-β1, PERK, and connexin 43 proteins, and kallikrein mRNA in SHRs, along with decreased inflammation and apoptosis.

Keyword

Spontaneously hypertensive rats; Losartan; Gene expression

MeSH Terms

Adult
Angiotensins
Animals
Apoptosis
Blotting, Western
Connexin 43
Extracellular Signal-Regulated MAP Kinases
Gene Expression
Heart Ventricles*
Humans
Inflammation
Kallikreins
Losartan*
Male
Monocytes
Polymerase Chain Reaction
Rats
Rats, Inbred SHR*
Reverse Transcription
RNA, Messenger
Transforming Growth Factors
Angiotensins
Connexin 43
Extracellular Signal-Regulated MAP Kinases
Kallikreins
Losartan
RNA, Messenger
Transforming Growth Factors