Renin-angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation

Chia Ti Tsai, Ling Ping Lai, Juey Jen Hwang, Wen Pin Chen, Fu Tien Chiang, Kuan Lih Hsu, Chuen Den Tseng, Yung Zu Tseng, Jiunn Lee Lin

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

OBJECTIVES: Local atrial tissue angiotensin II (AngII) level is elevated in atrial fibrillation (AF), but the mechanism is unknown. We hypothesized that atrial myocytes express all components of the renin-angiotensin system (RAS) and investigated whether rapid depolarization alone is sufficient to increase paracrine AngII production by up-regulating RAS component expression. METHODS: In the HL-1 atrial cell line, rapid depolarization was induced by rapid field electrical stimulation (RES) at 1.0 V/cm and 600/min (10 Hz) in atrial HL-1 cells. In a pig model of AF, AF was induced by atrial pacing at 600/min in 10 adult pigs and 10 sham-operated pigs for comparison. RESULTS: In atrial myocytes, RES induced a sustained elevation of intracellular calcium, and up-regulation of angiotensin-converting enzyme (ACE), chymase and angiotensinogen, resulting in increased AngII production. RES-induced AngII production was attenuated by enalapril [ACE inhibitor (ACEI)] and chymostatin (chymase inhibitor). Conditioned medium from RES-stimulated atrial myocytes increased [H]leucine uptake and atrial natriuretic peptide expression in atrial myocytes, and [H]proline uptake and collagen type 1 alpha 1 expression in atrial fibroblasts. Both were attenuated by co-incubation with the AngII type 1 receptor blocker (ARB) losartan. In the porcine model, significant structural changes and a similar pattern of changes of RAS components were noted in AF pigs. CONCLUSIONS: Atrial cells expressed all components of RAS and rapid depolarization alone was sufficient to up-regulate RAS components, increase paracrine AngII production and induce atrial structural changes, which are attenuated by ACEI, ARB and chymase inhibitor.

Original languageEnglish
Pages (from-to)570-582
Number of pages13
JournalJournal of Hypertension
Volume26
Issue number3
DOIs
Publication statusPublished - Mar 1 2008
Externally publishedYes

Fingerprint

Renin-Angiotensin System
Angiotensin II
Atrial Fibrillation
Chymases
Swine
Muscle Cells
Electric Stimulation
Cell Line
Angiotensin-Converting Enzyme Inhibitors
Up-Regulation
Angiotensin II Type 1 Receptor Blockers
Angiotensinogen
Enalapril
Losartan
Atrial Natriuretic Factor
Peptidyl-Dipeptidase A
Conditioned Culture Medium
Collagen Type I
Proline
Leucine

Keywords

  • Angiotensin II
  • Atrial fibrillation
  • Atrial fibroblast
  • Atrial myocyte
  • Rapid depolarization
  • Rapid pacing
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Renin-angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation. / Tsai, Chia Ti; Lai, Ling Ping; Hwang, Juey Jen; Chen, Wen Pin; Chiang, Fu Tien; Hsu, Kuan Lih; Tseng, Chuen Den; Tseng, Yung Zu; Lin, Jiunn Lee.

In: Journal of Hypertension, Vol. 26, No. 3, 01.03.2008, p. 570-582.

Research output: Contribution to journalArticle

Tsai, Chia Ti ; Lai, Ling Ping ; Hwang, Juey Jen ; Chen, Wen Pin ; Chiang, Fu Tien ; Hsu, Kuan Lih ; Tseng, Chuen Den ; Tseng, Yung Zu ; Lin, Jiunn Lee. / Renin-angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation. In: Journal of Hypertension. 2008 ; Vol. 26, No. 3. pp. 570-582.
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T1 - Renin-angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation

AU - Tsai, Chia Ti

AU - Lai, Ling Ping

AU - Hwang, Juey Jen

AU - Chen, Wen Pin

AU - Chiang, Fu Tien

AU - Hsu, Kuan Lih

AU - Tseng, Chuen Den

AU - Tseng, Yung Zu

AU - Lin, Jiunn Lee

PY - 2008/3/1

Y1 - 2008/3/1

N2 - OBJECTIVES: Local atrial tissue angiotensin II (AngII) level is elevated in atrial fibrillation (AF), but the mechanism is unknown. We hypothesized that atrial myocytes express all components of the renin-angiotensin system (RAS) and investigated whether rapid depolarization alone is sufficient to increase paracrine AngII production by up-regulating RAS component expression. METHODS: In the HL-1 atrial cell line, rapid depolarization was induced by rapid field electrical stimulation (RES) at 1.0 V/cm and 600/min (10 Hz) in atrial HL-1 cells. In a pig model of AF, AF was induced by atrial pacing at 600/min in 10 adult pigs and 10 sham-operated pigs for comparison. RESULTS: In atrial myocytes, RES induced a sustained elevation of intracellular calcium, and up-regulation of angiotensin-converting enzyme (ACE), chymase and angiotensinogen, resulting in increased AngII production. RES-induced AngII production was attenuated by enalapril [ACE inhibitor (ACEI)] and chymostatin (chymase inhibitor). Conditioned medium from RES-stimulated atrial myocytes increased [H]leucine uptake and atrial natriuretic peptide expression in atrial myocytes, and [H]proline uptake and collagen type 1 alpha 1 expression in atrial fibroblasts. Both were attenuated by co-incubation with the AngII type 1 receptor blocker (ARB) losartan. In the porcine model, significant structural changes and a similar pattern of changes of RAS components were noted in AF pigs. CONCLUSIONS: Atrial cells expressed all components of RAS and rapid depolarization alone was sufficient to up-regulate RAS components, increase paracrine AngII production and induce atrial structural changes, which are attenuated by ACEI, ARB and chymase inhibitor.

AB - OBJECTIVES: Local atrial tissue angiotensin II (AngII) level is elevated in atrial fibrillation (AF), but the mechanism is unknown. We hypothesized that atrial myocytes express all components of the renin-angiotensin system (RAS) and investigated whether rapid depolarization alone is sufficient to increase paracrine AngII production by up-regulating RAS component expression. METHODS: In the HL-1 atrial cell line, rapid depolarization was induced by rapid field electrical stimulation (RES) at 1.0 V/cm and 600/min (10 Hz) in atrial HL-1 cells. In a pig model of AF, AF was induced by atrial pacing at 600/min in 10 adult pigs and 10 sham-operated pigs for comparison. RESULTS: In atrial myocytes, RES induced a sustained elevation of intracellular calcium, and up-regulation of angiotensin-converting enzyme (ACE), chymase and angiotensinogen, resulting in increased AngII production. RES-induced AngII production was attenuated by enalapril [ACE inhibitor (ACEI)] and chymostatin (chymase inhibitor). Conditioned medium from RES-stimulated atrial myocytes increased [H]leucine uptake and atrial natriuretic peptide expression in atrial myocytes, and [H]proline uptake and collagen type 1 alpha 1 expression in atrial fibroblasts. Both were attenuated by co-incubation with the AngII type 1 receptor blocker (ARB) losartan. In the porcine model, significant structural changes and a similar pattern of changes of RAS components were noted in AF pigs. CONCLUSIONS: Atrial cells expressed all components of RAS and rapid depolarization alone was sufficient to up-regulate RAS components, increase paracrine AngII production and induce atrial structural changes, which are attenuated by ACEI, ARB and chymase inhibitor.

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KW - Atrial fibrillation

KW - Atrial fibroblast

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KW - Angiotensin ii

KW - Atrial fibrillation

KW - Atrial fibroblast

KW - Atrial myocyte

KW - Rapid depolarization

KW - Rapid pacing

KW - Renin-angiotensin system

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