Arachidonate metabolism in cultured fibroblasts derived from normal and infarcted canine heart.

Weber, D.; Stroud, Eric D.; Prescott, Stephen M.

doi:10.1161/01.res.65.3.671

Cited by 19 publications

(11 citation statements)

References 37 publications

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“…In patients with acute myocardial infarction who are not receiving a thrombolytic agent, PGI2 formation rose over the 48 hours after admission and gradually declined toward normal by day 5.5,14,40 This activity correlated closely with plasma CPK level, and striking increases occurred in patients with large myocardial infarctions, findings that suggest that the increase in PG12 biosynthesis derives from the heart.14,41 The cellular origin is uncertain, but it is probably vascular endothelium because isolated myocardial cells have no prostaglandin synthase activity and endothelial cells are the major source of PGI2 in myocardial tissue.42 Furthermore, injured myocytes release arachidonic acid,43 which may be metabolized by other cells to form prostaglandins including PGI2. 44 Although the number of patients was small, a similar increase in PGI2 was seen in patients who failed to reperfuse after t-PA administration. In contrast, the increase in PGI2 biosynthesis was blunted in patients who reperfused, and it did not correlate with plasma CPK.…”

Section: Resultsmentioning

confidence: 82%

Platelet and vascular function during coronary thrombolysis with tissue-type plasminogen activator.

et al. 1989

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Platelet activation may limit the response to tissue-type plasminogen activator (t-PA) during coronary thrombolysis in humans. As an index of platelet activation, we assessed thromboxane A2 biosynthesis during coronary thrombolysis with intravenous t-PA in patients with acute myocardial infarction. Urinary 2,3-dinor-thromboxane B2, a metabolite of thromboxane A2, was increased to a peak of 3,327+±511 pg/mg creatinine (n=12) following administration of intravenous t-PA and remained elevated for 48 hours. This increase was abolished by pretreatment with aspirin 325 mg orally (n=6), indicating de novo biosynthesis of thromboxane A2 rather than washout of preformed metabolites during reperfusion. Prostacyclin (PGI2) biosynthesis, determined by excretion of 2,3-dinor-6-keto-PGFia, also increased after t-PA administration. However, this increase was less pronounced in patients who reperfused (28+±3.3 ng.hr/mg creatinine) than in patients who failed to reperfuse (118+±30 ng-hr/mg creatinine, p<0.05). These data provide evidence of platelet activation during coronary thrombolysis with t-PA. In patients who reperfuse, the reduction in PGI2 biosynthesis may be a marker of reperfusion injury to the vasculature and may further amplify platelet activation. (Circulation 1989;80:1718-1725 P latelet activation plays a major role in limiting the response to tissue-type plasminogen activator (t-PA) in experimental models of coronary thrombosis.1-4 In particular, platelets delay reperfusion and induce reocclusion.1,4 Platelet activation is also increased in patients with acute myocardial infarction treated with intravenous streptokinase,5 and antiplatelet therapy enhances the response to streptokinase, accelerating reperfusion6 and further reducing mortality.7 However, streptokinase directly activates human platelets.5 In contrast, t-PA inhibits platelet function in vitro.8 Although t-PA has been reported to increase platelet aggregation ex vivo,9 this increase may reflect an

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Section: Resultsmentioning

confidence: 82%

Platelet and vascular function during coronary thrombolysis with tissue-type plasminogen activator.

et al. 1989

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“…Although these results point to a possible role for PGs in the regulation of cardiac growth, other cardiovascular effects such as a reduction in blood viscosity (18) cannot be ruled out. Prostaglandin synthesis is also greater in cardiomyocytes (47), endothelial cells (48) and fibroblasts (49) subjected to hypoxia. The role of PGF 2␣ in hypoxia may be to aid recovery of injured myocytes by stimulating protein synthesis, as well as to stimulate growth of uninjured myocytes to restore a decrement in myocardial contractility.…”

Section: Discussionmentioning

confidence: 97%

Prostaglandin F2α Stimulates Hypertrophic Growth of Cultured Neonatal Rat Ventricular Myocytes

Adams

Migita²,

Yu³

et al. 1996

Journal of Biological Chemistry

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During embryonic development the myocardium enlarges by the proliferation of cardiac myocytes. Shortly after birth, cardiac myocytes lose their capacity for mitogenesis, and further growth of the myocardium to meet the increasing hemodynamic demand of an elevated blood pressure and blood volume occurs by enlargement of existing muscle cells (hypertrophy). Similarly, the restoration of myocardial contractile performance lost to ischemia or viral infection is dependent on the recovery of injured myocytes and on the compensatory enlargement of agonist myocytes. Thus, an understanding of the controlling factors of myocardial protein synthesis and growth has implications for cardiac ontogeny, adaptation to chronic physiologic and pathophysiologic stimuli, and recovery from injury.Cardiac hypertrophy is produced by a variety of stimuli in culture and in vivo (1), including, but not limited to, mechanical stretch (2, 3), neurotransmitters (4, 5), and hormones (6, 7). As the biochemistry of myocardial growth is experimentally revealed, some common intracellular signaling pathways appear among primary stimuli. For example, stretch-induced cardiomyocyte hypertrophy is mediated, in part, by the local production of angiotensin II (8), and several hypertrophic stimuli, angiotensin II, norepinephrine, and endothelin-1, act through G q protein-coupled receptors (9 -11) and activate mitogen-activated protein kinases (12, 13). Direct evidence of G q involvement in cardiac growth was provided by microinjection of G q neutralizing antibodies to block the hypertrophic response of neonatal rat ventricular myocytes to the ␣ 1 -adrenergic agonist phenylephrine (9). Thus cardiac hypertrophy appears to be mediated, at least for several stimuli, by agonists of G q proteincoupled receptors.In addition to promoting myocardial growth, angiotensin II, norepinephrine, and endothelin-1 are vasoactive substances. Interestingly, Katz (14) speculated that angiotensin II evolved from a primitive growth factor and assumed additional regulatory roles in the cardiovascular system, such as stimulation of aldosterone production and smooth muscle contraction. It is conceivable that other vasoactive substances went through a similar evolutionary process, especially in consideration of the finding that Ca 2ϩ signaling is important for angiotensin II activation of mitogen-activated protein kinase in cardiac myocytes (13).Prostaglandin F 2␣ (PGF 2␣ ) 1 is a vasoactive substance that stimulates protein synthesis in skeletal and smooth muscle cells in culture (15,16). Moreover, PGF 2␣ regulates, in part, stretch-induced skeletal myoblast growth (16), and the effects of exogenous PGF 2␣ on vascular smooth muscle hypertrophy are most likely mediated by a PGF-specific receptor (15). As to the heart, PGF 2␣ was increased in the left ventricles of rabbits by acute pressure overload (17), and PG synthase inhibitors blocked cardiac growth induced by hypertension (18) and clenbuterol (19). These observations and others suggested that PGF 2␣ may play a role in the con...

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“…Furthermore, isolated canine cardiac fibroblast-like cells were found to have greater cyclooxygenase activity and PGE 2 production in the infarcted tissue compared with fibroblasts of the noninfarcted tissue. 9 Recently, Siragy et al 10 demonstrated that Agtr2Ϫ/Y mice, compared with wild-type (WT) mice, had higher basal levels of PGE 2 and lower prostaglandin F 2␣ (PGF 2␣ ) levels in renal interstitial fluid under basal or dietary sodium restriction. Given the appearance of PGs in inflammatory cells in healing wound, these observations suggest possible differences in the response of heart to infarction in AT 2 gene-deleted mice.…”

Section: See P 2167mentioning

confidence: 99%

Targeted Deletion of Angiotensin II Type 2 Receptor Caused Cardiac Rupture After Acute Myocardial Infarction

et al. 2002

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Background-Accumulating evidence has suggested that the cardiac renin-angiotensin system is activated during the remodeling process after myocardial infarction (MI). Although 2 types of angiotensin II receptors (AT 1 and AT 2 ) are upregulated in the infarcted tissue, the contribution of AT 2 to the subsequent fibrogenetic phase of wound healing is less certain. This study was conducted to evaluate the role of AT 2 in wound healing after MI using an in vivo intervention study in mice with MI. Methods and Results-We examined myocardial hypertrophy, cardiac fibrosis, and morphological evidence of fibrillar collagen accumulation at the infarcted and noninfarcted regions in male mice lacking the AT 2 receptor (Agtr2Ϫ/Y) and age-matched wild-type (WT) animals. Of the Agtr2Ϫ/Y mice, 63.6% died of cardiac rupture, whereas 23.5% of the WT mice died of the same cause within 1 week. The extent of fibrosis and that of collagen gene expression in Agtr2Ϫ/Y mice were significantly reduced compared with WT mice at 1 week after coronary ligation. Furthermore, MI resulted in a marked increase in the prostaglandin E 2 (PGE 2 ) level at 4 days after surgery in Agtr2Ϫ/Y mice. In WT mice, the PGE 2 level was also elevated after MI but to a significantly lesser extent than in Agtr2Ϫ/Y mice. Conclusions-A chronic loss of AT 2 by gene targeting prevented the collagen deposition and caused cardiac rupture. The markedly elevated PGE 2 may be a mechanism that inhibits collagen synthesis in the infarcted region of Agtr2Ϫ/Y mice.

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Arachidonate metabolism in cultured fibroblasts derived from normal and infarcted canine heart.

Cited by 19 publications

References 37 publications

Platelet and vascular function during coronary thrombolysis with tissue-type plasminogen activator.

Platelet and vascular function during coronary thrombolysis with tissue-type plasminogen activator.

Prostaglandin F2α Stimulates Hypertrophic Growth of Cultured Neonatal Rat Ventricular Myocytes

Targeted Deletion of Angiotensin II Type 2 Receptor Caused Cardiac Rupture After Acute Myocardial Infarction

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