Korean Circ J.  1999 Jan;29(1):84-95. 10.4070/kcj.1999.29.1.84.

The Effects of Aldosterone and Cytokines IL-1beta, TNF-alpha on the Expression of Angiotensin Converting Enzyme Gene in Vascular Smooth Muscle Cells

• Kim DK
• Huh JE
• Choe YH
• Park SJ
• Jung EA
• Byun J
• Gwon HC
• Park SW
• Kim JS
• Lee SH
• Hong KP
• Park JE
• Seo JD
• Lee WR

• KMID: 1858334
• DOI: http://doi.org/10.4070/kcj.1999.29.1.84

Abstract

BACKGROUND
It has been suggested that all components of the renin-angiotensin-aldosterone system (RAAS) are present in the vascular wall and that the vascular RAAS modulates vascular tone and vascular hypertrophy. One of the catalytic step in the RAAS cascade is the local conversion of angiotensin I to angiotensin II (Ang II) by angiotensin converting enzyme (ACE). One of the major sources of ACE in the vasculature is vascular smooth muscle cells (VSMC). Here, we provide insight into the intrinsic mechanisms by which the components of RAAS regulate gene expression of ACE in cultured smooth muscle cells of the rat and we also investigated the effects of cytokines on ACE mRNA.
METHODS
RNA was extracted from the primary cultured VSMCs. We analyzed the expression levels of ACE by competitive reverse transcription-PCR using recombinant RNA as an internal standard.
RESULTS
1) ACE mRNA level was increased markedly by aldosterone in a dose- and time-dependent manner, indicating that there exists positive feedback mechanism within RAAS. 2) The induction of ACE mRNA by aldosterone was inhibited by spironolactone. 3) Aldosterone-stimulated expression of ACE was also inhibited by Ang II, which shows that Ang II acts as a negative regulator of the expression of ACE in RAAS cascade. 4) Interleukin-1beta or TNF-alpha did not induce ACE mRNA expression. 5) However, mixture of interleukin-1betaand TNF-alpha(CytoMix) significantly increased the expression of ACE. It was also shown that CytoMix increased aldosterone-stimulated ACE mRNA expression in an additative manner.
CONCLUSION
These results indicate that the expression of ACE in smooth muscle cells is modulated by the components of RAAS and cytokines. The intrinsic positive and negative feedback controls of RAAS would play an important role in the pathogenesis of vascular diseases.

Keyword

Angiotensin converting enzyme (ACE); Gene expression; Aldosterone; Renin-angiotensin-aldosterone system (RAAS); TNF-alpha

MeSH Terms

Aldosterone*
Angiotensin I
Angiotensin II
Angiotensins*
Animals
Cytokines*
Gene Expression
Hypertrophy
Interleukin-1beta
Muscle, Smooth, Vascular*
Myocytes, Smooth Muscle
Peptidyl-Dipeptidase A*
Rats
Renin-Angiotensin System
RNA
RNA, Messenger
Spironolactone
Tumor Necrosis Factor-alpha*
Vascular Diseases
Aldosterone
Angiotensin I
Angiotensin II
Angiotensins
Cytokines
Interleukin-1beta
Peptidyl-Dipeptidase A
RNA
RNA, Messenger
Spironolactone
Tumor Necrosis Factor-alpha