A novel, simple bioactivity assay for relaxin based on inhibition of platelet aggregation

Bani, Danièle; Nistri, Silvia; Cinci, Lorenzo; Giannini, Lucia; Princivalle, M; Elliott, Lucy; Bigazzi, Mario; Masini, Emanuela

doi:10.1016/j.regpep.2007.05.004

Cited by 21 publications

(17 citation statements)

References 28 publications

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“…34 Indeed, a bioactivity assay for RLN has been based upon its inhibition of platelet aggregation. 35 Thus, a potential mechanism of action of the increased RLN in these tissues in placenta accreta suggests that RLN may be the cause of the excessive bleeding in these patients. Because RLN also increases the expression of the MMPs, 17 we sought changes here in MMP-2 and MMP-9 gene expression in the same samples.…”

Section: Discussionmentioning

confidence: 99%

“…All tissues were examined histologically by a pathologist to eliminate any tissue with a pathology not identified clinically. Tissues from 6 patients with placenta accreta were obtained (30)(31)(32)(33)(34)(35)(36) weeks of gestation at time of delivery/hysterectomy) and all of these patients had placenta previa. These patients were matched as closely as possible to similar gestational-age controls from the gestation study.…”

Section: Patient Selection and Tissue Collectionmentioning

confidence: 99%

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Relaxin, Its Receptor (RXFP1), and Insulin-Like Peptide 4 Expression Through Gestation and in Placenta Accreta

et al. 2013

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This study was designed to show whether placental relaxin (RLN), its receptor (RXFP1), or insulin-like peptide 4 (INSL4) might have altered expression in patients with placenta accreta. The baseline expression of their genes through gestation (n ¼ 34) was quantitated in the placental basal plate (BP) and villous trophoblast (TR), and compared to their expression in placenta accreta (n ¼ 6). The proteins were also immunolocalized and quantitated in the accreta tissues. The messenger RNAs (mRNAs) of matrix metalloproteinase 9, -2, and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were also measured. Results demonstrated that the BP and TR expressed low levels of RLN/RXFP1 and INSL4 through gestation. In accreta, increased RLN gene and protein in BP were associated with antepartum bleeding whereas INSL4 expression decreased throughout the TR. There were no changes in mRNAs for MMPs, but TIMP-1 was increased only in the invasive TR.

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Section: Discussionmentioning

confidence: 99%

Section: Patient Selection and Tissue Collectionmentioning

confidence: 99%

Relaxin, Its Receptor (RXFP1), and Insulin-Like Peptide 4 Expression Through Gestation and in Placenta Accreta

et al. 2013

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“…Using human platelets, which are specific and sensitive targets for RLX, as in vitro bioactivity test system [58], we observed that pRLX is significantly more potent than equimolar doses of human recombinant H2 RLX in terms of inhibition of platelet aggregation (approximately 150% of the effects of H2 RLX with 100 ng/ml). The explanation of this discrepancy remains a matter of speculation: in fact, although pRLX has been shown to have lower affinity than H2 RLX for human RXFP1 [59], it cannot be ruled out that it could effectively bind to and stimulate multiple RLX receptors, such as RXFP1 and RXFP2, at variance with H2 RLX which chiefly binds to RXFP1.…”

Section: Rlxmentioning

confidence: 98%

Relaxin as a Cardiovascular Drug: A Promise Kept

Bani¹,

Bigazzi

2011

CDS

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Relaxin (RLX), formerly known for its effects on reproduction and pregnancy, has been later shown to be a pleiotropic hormone, capable of also targeting numerous non-reproductive organs of the cardiovascular, nervous, respiratory, tegumental, excretory and digestive systems. Most of these effects have been studied in animal models, but there is compelling evidence that RLX also acts in humans. In more recent years, human luteal-type (H2) RLX synthesised by recombinant DNA technology has been investigated in clinical trials, mostly oriented to assess its therapeutic potential in cardiovascular disease. This indication was based on the accumulating pre-clinical evidence that RLX possesses prominent biological effects on systemic and coronary blood vessels, cardiomyocyte growth and differentiation, and cardiac/vascular connective tissue remodelling. This mini-review was intended as an update of our previous article that appeared in this journal in 2009, as the last 2 years have been characterised by fundamental achievements on the clinical profile of RLX. Eventually, after many years of inconclusive studies, RLX appears to be about to reach a recognised dignity as a cardiovascular drug.

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“…In fact, RLX has been shown to strongly inhibit the activation of neutrophils challenged in vitro with inflammatory mediators, by reducing oxidative burst, reactive oxygen species (ROS) generation and chemotaxis (Masini et al 2004). Finally, RLX has been reported to reduce markedly, and in a dose-dependent fashion, the aggregation of platelets (Bani et al 1995, 2007), which represents another pathogenic pillar of atherosclerosis. These multiple anti-inflammatory, anti-thrombotic effects of RLX rely on the stimulation of endogenous NO generation, but other concurrent mechanisms are likely to be involved.…”

Section: Relaxin and Vascular Dysfunctionmentioning

confidence: 99%

Relaxin as a natural agent for vascular health

Bani

2008

VHRM

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Hypertension, atherothrombosis, myocardial infarction, stroke, peripheral vascular disease, and renal failure are the main manifestations of cardiovascular disease (CVD), the leading cause of death and disability in developed countries. Continuing insight into the pathophysiology of CVD can allow identifi cation of effective therapeutic strategies to reduce the occurrence of death and/or severe disabilities. In this context, a healthy endothelium is deemed crucial to proper functioning and maintenance of anatomical integrity of the vascular system in many organs. Of note, epidemiologic studies indicate that the incidence of CVD in women is very low until menopause and increases sharply thereafter. The loss of protection against CVD in post-menopausal women has been chiefl y attributed to ovarian steroid defi ciency. However, besides steroids, the ovary also produces the peptide hormone relaxin (RLX), which provides potent vasoactive effects which render it the most likely candidate as the elusive physiological shield against CVD in fertile women. In particular, RLX has a specifi c relaxant effect on peripheral and coronary vasculature, exerted by the stimulation of endogenous nitric oxide (NO) generation by cells of the vascular wall, and can induce angiogenesis. Moreover, RLX inhibits the activation of infl ammatory leukocytes and platelets, which play a key role in CVD. Experimental studies performed in vascular and blood cell in vitro and in animal models of vascular dysfunction, as well as pioneer clinical observations, have provided evidence that RLX can prevent and/or improve CVD, thus offering background to clinical trials aimed at exploring the broad therapeutic potential of human recombinant RLX as a new cardiovascular drug.

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A novel, simple bioactivity assay for relaxin based on inhibition of platelet aggregation

Cited by 21 publications

References 28 publications

Relaxin, Its Receptor (RXFP1), and Insulin-Like Peptide 4 Expression Through Gestation and in Placenta Accreta

Relaxin, Its Receptor (RXFP1), and Insulin-Like Peptide 4 Expression Through Gestation and in Placenta Accreta

Relaxin as a Cardiovascular Drug: A Promise Kept

Relaxin as a natural agent for vascular health

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