Kinins in the Heart

Carretero, Oscar A.

doi:10.1007/978-1-59259-708-6_9

Cited by 5 publications

(4 citation statements)

References 97 publications

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“…However, in this model of heart failure after MI, ACE inhibitors, unlike Ac-SDKP, improved cardiac function. 12,40,[45][46][47][48][49] The mechanism of action of ACE inhibitors in heart failure is complex. In addition to blocking the conversion of angiotensin I to II, they also inhibit kinin hydrolysis and stimulate the release of nitric oxide, effects not seen with Ac-SDKP.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to blocking the conversion of angiotensin I to II, they also inhibit kinin hydrolysis and stimulate the release of nitric oxide, effects not seen with Ac-SDKP. 12,40,[45][46][47][48][49] In summary, Ac-SDKP prevented and reversed interstitial collagen and perivascular collagen deposition in the rat heart post-MI, associated with reduced macrophage infiltration and TGF-␤-positive cell expression. Our study suggests that the antifibrotic and anti-inflammatory effects of Ac-SDKP may be mediated in part by inhibition of macrophage infiltration and TGF-␤ expression.…”

Section: Discussionmentioning

confidence: 99%

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Ac-SDKP Reverses Inflammation and Fibrosis in Rats With Heart Failure After Myocardial Infarction

Yang¹,

Yang²,

Liu³

et al. 2004

Hypertension

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Abstract-Inflammation may play an important role in the pathogenesis of cardiac fibrosis in heart failure (HF) after myocardial infarction (MI). N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring antifibrotic peptide whose plasma concentration is increased 4-to 5-fold by angiotensin-converting enzyme inhibitors. We tested the hypothesis that in rats with HF after MI, Ac-SDKP acts as an anti-inflammatory cytokine, preventing and also reversing cardiac fibrosis in the noninfarcted area (reactive fibrosis), and thus affording functional improvement. We found that Ac-SDKP significantly decreased total collagen content in the prevention group from 23.7Ϯ0.9 to 15.0Ϯ0.7 g/mg and in the reversal group from 22.6Ϯ2. , PϽ0.01 (reversal). Ac-SDKP did not alter either blood pressure or left ventricular hypertrophy (LVH); however, it depressed systolic cardiac function in the prevention study while having no significant effect in the reversal group. We concluded that Ac-SDKP has an anti-inflammatory effect in HF that may contribute to its antifibrotic effect; however, this decrease in fibrosis without changes in LVH was not accompanied by an improvement in cardiac function. Key Words: rat Ⅲ myocardial infarction Ⅲ cardiac function Ⅲ collagen Ⅲ macrophages Ⅲ transforming growth factor-␤ N -acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring antifibrotic peptide whose plasma concentration is increased 4-to 5-fold by angiotensin-converting enzyme inhibitors. Ac-SDKP is released from its precursor thymosin-␤ 4 , which is present in most cells. 1 It inhibits pluripotent hematopoietic stem cell and hepatocyte proliferation by halting entry into the S phase of the cell cycle, maintaining cells in the G 0 /G 1 phase and thereby helping control their proliferation. [2][3][4] We have shown that in vitro Ac-SDKP inhibited cardiac fibroblast proliferation and collagen synthesis, 5 while in vivo it prevented collagen deposition in the left ventricle (LV) and kidneys in rats with aldosterone-salt hypertension and renovascular hypertension. 5,6 This decrease in collagen deposition was associated with a reduced number of proliferating cell nuclear antigen (PCNA)-positive cells, a marker of cell proliferation. These effects of Ac-SDKP occurred without changes in blood pressure or cardiomyocyte hypertrophy. Our studies suggest that one of the mechanisms by which Ac-SDKP prevents fibrosis is by inhibiting fibroblast proliferation and collagen synthesis. It is also known that inflammation plays a central role in the pathogenesis of interstitial and perivascular cardiac fibrosis in heart failure (HF) post-myocardial infarction (MI). Fibrosis is often co-localized with macrophages, which release cytokines such as transforming growth factor-␤ (TGF-␤) that play a crucial role in myocardial fibrosis. 7 There is evidence that Ac-SDKP inhibits TGF-␤ signal transduction through suppression of Smad2 phosphorylation. 8,9 However, it is not known whether it also inhibits the expression of TGF-␤.In the present study,...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ac-SDKP Reverses Inflammation and Fibrosis in Rats With Heart Failure After Myocardial Infarction

Yang¹,

Yang²,

Liu³

et al. 2004

Hypertension

Self Cite

122

121

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“…The BK B 1 receptor is only weakly expressed under physiological conditions, but is induced by inflammatory stimuli [17]. In contrast, the BK B 2 receptor, which is constitutively expressed in most tissues, is considered to be the major mediator of the BK-induced effects in the cardiovascular system [16,[18][19][20]. Protein and mRNA levels of both BK receptors are up-regulated in rat myocardium during the early phase following infarction, also suggesting that BK is involved in functional and structural alterations of the ischaemic myocardium [6,7].…”

Section: Introductionmentioning

confidence: 97%

“…The biological action of kinins is mediated by activation of at least two subtypes of G-protein-coupled BK receptors, B 1 and B 2 [14][15][16]. The BK B 1 receptor is only weakly expressed under physiological conditions, but is induced by inflammatory stimuli [17].…”

Section: Introductionmentioning

confidence: 99%

Lack of association of a 9 bp insertion/deletion polymorphism within the bradykinin 2 receptor gene with myocardial infarction

Fischer

Lieb²,

Marold

et al. 2004

Clinical Science

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The BK (bradykinin) B2 receptor is the major cellular mediator of the effects of BK. A 9 bp deletion in the promoter of the receptor gene represents an allelic variant that is associated with enhanced mRNA expression levels. We tested whether this polymorphism is associated with the prevalence of MI (myocardial infarction) or with echocardiographically determined left ventricular function in post-MI patients. Patients with documented MI (n=484), matched controls and controls without evidence of coronary heart disease (n=1363) constituted cases and controls. MI patients and controls were carefully matched for age, gender and cardiovascular risk factors. Genotype distributions of the 9 bp insertion/deletion polymorphism were similar across the groups: -9/-9, -9/+9 and +9/+9 were 22.1, 49.5 and 28.5% in MI patients, and 23.0, 44.6 and 32.5% in matched control subjects respectively. The lack of association was also observed in selected subgroups, stratified by age, gender and cardiovascular risk factors. Furthermore, there was no relation between this polymorphism and left ventricular systolic function in post-MI patients. These findings indicate that the 9 bp insertion/deletion polymorphism of the BK B2 receptor gene is neither related to the prevalence of MI nor to left ventricular function after MI.

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The Bradykinin B2 receptor is required for full expression of renal COX-2 and renin

et al. 2003

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Kinins in the Heart

Cited by 5 publications

References 97 publications

Ac-SDKP Reverses Inflammation and Fibrosis in Rats With Heart Failure After Myocardial Infarction

Ac-SDKP Reverses Inflammation and Fibrosis in Rats With Heart Failure After Myocardial Infarction

Lack of association of a 9 bp insertion/deletion polymorphism within the bradykinin 2 receptor gene with myocardial infarction

The Bradykinin B2 receptor is required for full expression of renal COX-2 and renin

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