Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat

Shanzana I. Khan, Waled A. Shihata, Karen L. Andrews, Man K. S. Lee, Xiao-Lei Moore, Ann-Maree Jefferis, Antony Vinh, Tracey Gaspari, Dragana Dragoljevic, Garry L. Jennings, Andrew J. Murphy, Jaye P. F. Chin-Dusting

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Despite its well-known antithrombotic properties, the effect of aspirin on blood pressure (BP) and hypertension pathology is unclear. The hugely varying doses used clinically have contributed to this confusion, with high-dose aspirin still commonly used due to concerns about the efficacy of low-dose aspirin. Because prostaglandins have been shown to both promote and inhibit T-cell activation, we also explored the immunomodulatory properties of aspirin in hypertension. Although the common preclinical high dose of 100 mg/kg/d improved vascular dysfunction and cardiac hypertrophy, this effect was accompanied by indices of elevated adaptive immunity, renal T-cell infiltration, renal fibrosis, and BP elevation in stroke-prone spontaneously hypertensive rats and in angiotensin II-induced hypertensive mice. The cardioprotective effects of aspirin were conserved with a lower dose (10 mg/kg/d) while circumventing heightened adaptive immunity and elevated BP. We also show that low-dose aspirin improves renal fibrosis. Differential inhibition of the COX-2 isoform may underlie the disparate effects of the 2 doses. Our results demonstrate the efficacy of low-dose aspirin in treating a vast array of cardiovascular parameters and suggest modulation of adaptive immunity as a novel mechanism underlying adverse cardiovascular profiles associated with COX-2 inhibitors. Clinical studies should identify the dose of aspirin that achieves maximal cardioprotection with a new awareness that higher doses of aspirin could trigger undesired autoimmunity in hypertensive individuals. This work also warrants an evaluation of high-dose aspirin and COX-2 inhibitor therapy in sufferers of inflammatory conditions who are already at increased risk for cardiovascular disease.

Original languageEnglish
Pages (from-to)1510-1521
Number of pages12
JournalFASEB Journal
Volume33
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Cardiac hypertrophy
  • Cyclooxygenase
  • Prostanoids
  • Renal fibrosis
  • Vascular function

Cite this

Khan, Shanzana I. ; Shihata, Waled A. ; Andrews, Karen L. ; Lee, Man K. S. ; Moore, Xiao-Lei ; Jefferis, Ann-Maree ; Vinh, Antony ; Gaspari, Tracey ; Dragoljevic, Dragana ; Jennings, Garry L. ; Murphy, Andrew J. ; Chin-Dusting, Jaye P. F. / Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat. In: FASEB Journal. 2019 ; Vol. 33, No. 1. pp. 1510-1521.
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Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat. / Khan, Shanzana I.; Shihata, Waled A.; Andrews, Karen L.; Lee, Man K. S.; Moore, Xiao-Lei; Jefferis, Ann-Maree; Vinh, Antony; Gaspari, Tracey; Dragoljevic, Dragana; Jennings, Garry L.; Murphy, Andrew J.; Chin-Dusting, Jaye P. F.

In: FASEB Journal, Vol. 33, No. 1, 01.01.2019, p. 1510-1521.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Khan, Shanzana I.

AU - Shihata, Waled A.

AU - Andrews, Karen L.

AU - Lee, Man K. S.

AU - Moore, Xiao-Lei

AU - Jefferis, Ann-Maree

AU - Vinh, Antony

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AU - Dragoljevic, Dragana

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AU - Murphy, Andrew J.

AU - Chin-Dusting, Jaye P. F.

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