Influence of serum cholesterol on atherogenesis and intimal hyperplasia after angioplasty

Inhibition by amlodipine

Mark B. Kahn, Kathleen Boesze-Battaglia, David W Stepp, Artium Petrov, Yong Huang, R. Preston Mason, Thomas N. Tulenko

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The objectives of the present study were to determine whether serum hypercholesterolemia (HC) promotes the development of spontaneous and angioplasty-induced lesions and whether amlodipine inhibits these lesions and cellular processes underlying their genesis. Rabbits were fed normal, 0.5%, or 2% cholesterol diets for 9 wk, which resulted in the development of increasing HC. After week one, balloon dilation of the abdominal aorta was performed while the thoracic aorta was not disturbed and monitored for the development of spontaneous lesions. Lesion size increased with the degree of HC and was accompanied by increased collagen synthesis and smooth muscle cell (SMC) proliferation at each site. Amlodipine (5 mg/kg po) inhibited lesion size by 50% (P < 0.01) at both sites in cholesterol-fed animals but not at angioplasty sites in animals on a normal diet. Local collagen synthesis was inhibited at both sites by amlodipine in the diet animals. The increase in HC was accompanied by a 1.7-fold increase in basal Ca 2+ uptake in SMCs in the thoracic aorta, which was not altered by amlodipine, nifedipine, Ni 2+, or La 3+, revealing an uninhibitable calcium leak during atherogenesis. In culture, cholesterol enrichment increased SMC proliferation, collagen synthesis, and the secretion of a soluble SMC mitogen, which were inhibited by amlodipine (10 -9 M). Finally, in SMC membranes, amlodipine uniquely restored the cholesterol-expanded membrane bilayer width without any effect on membrane fluidity. This study establishes a causal role between serum HC and the development of spontaneous and angioplasty-induced lesions and the ability of amlodipine to disrupt this action by a novel remodelling action on the SMC membrane.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number2 57-2
DOIs
StatePublished - Feb 1 2005

Fingerprint

Tunica Intima
Amlodipine
Angioplasty
Hyperplasia
Atherosclerosis
Cholesterol
Hypercholesterolemia
Smooth Muscle Myocytes
Serum
Collagen
Diet
Thoracic Aorta
Cell Proliferation
Cell Membrane
Membrane Fluidity
Abdominal Aorta
Nifedipine
Mitogens
Dilatation
Rabbits

Keywords

  • Arteries
  • Atherosclerosis
  • Low-density lipoproteins
  • Membranes
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Influence of serum cholesterol on atherogenesis and intimal hyperplasia after angioplasty : Inhibition by amlodipine. / Kahn, Mark B.; Boesze-Battaglia, Kathleen; Stepp, David W; Petrov, Artium; Huang, Yong; Mason, R. Preston; Tulenko, Thomas N.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 2 57-2, 01.02.2005.

Research output: Contribution to journalArticle

Kahn, Mark B. ; Boesze-Battaglia, Kathleen ; Stepp, David W ; Petrov, Artium ; Huang, Yong ; Mason, R. Preston ; Tulenko, Thomas N. / Influence of serum cholesterol on atherogenesis and intimal hyperplasia after angioplasty : Inhibition by amlodipine. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 288, No. 2 57-2.
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