Peptide leukotriene receptor antagonism in myocardial ischaemia and reperfusion

Hock, Carl E.; Beck, Leslie D.; Papa, Louis A.

doi:10.1093/cvr/26.12.1206

Cited by 33 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased TXA 2 is associated with pulmonary fibrosis (12), whereas experiments using fibroblasts overexpressing 12-lipoxygenase have shown that these cells synthesize greater amounts of collagen I (13), the predominant type of collagen found in the heart and primarily responsible for cardiac fibrosis and increased myocardial stiffness (1). Furthermore, antagonism of LTD 4 /E 4 receptors during myocardial reperfusion reduced the size of the necrotic site and preserved cardiac function (46).…”

Section: Discussionmentioning

confidence: 99%

Antifibrotic Activity of an Inhibitor of Group IIA Secretory Phospholipase A2 in Young Spontaneously Hypertensive Rats

Levick¹,

Loch²,

Rolfe³

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

The development of fibrosis in the chronically hypertensive heart is associated with infiltration of inflammatory cells and cardiac hypertrophy. In this study, an inhibitor of the proinflammatory enzyme, group IIA human secretory phospholipase A2 (sPLA2-IIA), has been found to prevent collagen deposition as an important component of cardiovascular remodeling in a rat model of developing chronic hypertension. Daily treatment of young male spontaneously hypertensive rats (SHR) with an sPLA2-IIA inhibitor (KH064, 5-(4-benzyloxyphenyl)-4S-(phenyl-heptanoylamino)-pentanoic acid, 5 mg/kg/day p.o.) prevented increases in the content of perivascular (SHR 20.6 ± 0.9%, n = 5; SHR+KH064 14.0 ± 1.2%, n = 5) and interstitial (SHR 7.9 ± 0.3%, n = 6; SHR+KH064 5.4 ± 0.7%, n = 6) collagen in the left ventricle of rat hearts, but did not affect numbers of infiltrating monocytes/macrophages, left ventricular hypertrophy (SHR 2.88 ± 0.08, n = 12; SHR+KH064 3.09 ± 0.08 mg/g body weight, n = 9), increased systolic blood pressure, or thoracic aortic responses. This selective antifibrotic activity suggests that sPLA2-IIA may have an important but specific role in cardiac fibrosis, and that its inhibitors could be useful in dissecting molecular pathways leading to fibrotic conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Antifibrotic Activity of an Inhibitor of Group IIA Secretory Phospholipase A2 in Young Spontaneously Hypertensive Rats

Levick¹,

Loch²,

Rolfe³

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…LTD 4 /LTE 4 receptor antagonism reduced the extent of myocardial necrosis in a feline model of ischemia-reperfusion injury (68). Although, Hahn et al (69) found that CysLT receptor antagonism was not able to alter infarct size in coronary artery ligated dogs.…”

Section: Lo Metabolismmentioning

confidence: 97%

Arachidonic Acid Metabolism as a Potential Mediator of Cardiac Fibrosis Associated with Inflammation

Levick

Loch

Taylor

et al. 2007

The Journal of Immunology

101

View full text Add to dashboard Cite

An increase in left ventricular collagen (cardiac fibrosis) is a detrimental process that adversely affects heart function. Strong evidence implicates the infiltration of inflammatory cells as a critical part of the process resulting in cardiac fibrosis. Inflammatory cells are capable of releasing arachidonic acid, which may be further metabolized by cyclooxygenase, lipoxygenase, and cytochrome P450 monooxygenase enzymes to biologically active products, including PGs, leukotrienes, epoxyeicosatrienoic acids, and hydroxyeicosatetraenoic acids. Some of these products have profibrotic properties and may represent a pathway by which inflammatory cells initiate and mediate the development of cardiac fibrosis. In this study, we critically review the current literature on the potential link between this pathway and cardiac fibrosis.

show abstract

“…However, the role of CysLT 1 R in CVDs is rather controversial. Findings suggesting a role for cysteinyl LTs in the extension of ischemic damage and in cardiac dysfunction during reperfusion (Toki et al, 1988;Hock et al, 1992) are evenly balanced by results suggesting that these autacoids have no (Hahn et al, 1992) or little (Ito et al, 1989) contribution to the progression of myocardial ischemia-reperfusion injury. On the other hand, the LTRAs investigated in these studies belong to the first generation of molecules and may have not displayed enough potency to compete with the endogenous ligands, which are likely to be present with very high local bioavailability at sites where inflammatory cell accumulation and myocardial injury take place.…”

Section: New Potential Therapeutic Applications Of Leukotriene Recmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Bäck¹,

Dahlén²,

Drazen³

et al. 2011

Pharmacol Rev

130

View full text Add to dashboard Cite

Peptide leukotriene receptor antagonism in myocardial ischaemia and reperfusion

Abstract: LY-171883 has a protective effect in ischaemia-reperfusion injury to the myocardium. These findings suggest a role for peptide leukotrienes both in the extension of ischaemic damage and in post-ischaemic ventricular dysfunction during reperfusion.

Cited by 33 publications

References 0 publications

Antifibrotic Activity of an Inhibitor of Group IIA Secretory Phospholipase A2 in Young Spontaneously Hypertensive Rats

Antifibrotic Activity of an Inhibitor of Group IIA Secretory Phospholipase A2 in Young Spontaneously Hypertensive Rats

Arachidonic Acid Metabolism as a Potential Mediator of Cardiac Fibrosis Associated with Inflammation

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Contact Info

Product

Resources

About