Implications of proprotein Convertase 5 (PC5) in the arterial restenotic process in a porcine model

Veinot, John P.; Prichett-Pejic, Wendy; Picard, Pierre; Parks, William; Schwartz, Robert S.; Seidah, Nabil G.; Chrétien, Michel

doi:10.1016/j.carpath.2004.05.004

Cited by 8 publications

(5 citation statements)

References 58 publications

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ AMH belongs to the transforming growth factor-beta (TGF-β) superfamily that includes TGF-β and bone morphogenetic proteins (BMPs). It is secreted as proAMH and is cleaved by enzymes found in vascular tissues 15,16 . Once cleaved, it binds and activates non-specific receptors (AMH type I or activin receptor-like protein kinases [ALK2, ALK3, or ALK6]) or specific receptor (AMHRII).…”

Section: Discussionmentioning

confidence: 99%

Association of Anti-Mullerian Hormone with C-Reactive Protein in Men

Kadariya

Kurbanova

Qayyum

2019

Sci Rep

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While serum anti-mullerian hormone (AMH) levels are inversely associated with all-cause mortality in men, the underlying mechanisms are unclear. Elevated levels of inflammation, also associated with allcause mortality, and may be the link between AMH and mortality. Hence, we examined the association of AMH with serum c-reactive protein (CRP), a biomarker of inflammation, in men. We included men ≥20 years from the National Health and Nutrition Examination Survey (1999-2004). We used survey weight-adjusted linear regression to examine the association between AMH and cRp without and with adjustment for age, race, body mass index (BMi), smoking, hypertension, diabetes, cholesterol, glomerular filtration rate (GFR), testosterone, androstenedione, and sex hormone binding globulin. Of the 949 men, 212 (22%) were elderly, 493 (52%) Caucasian, 254 (27%) current smokers, 100 (10%) diabetics, and 312 (33%) had hypertension. Mean (SD) AMH was 8.4 (7.2) ng/mL and median (IQR) CRP level was 0.17 (3) mg/L. Using linear regression, each 10 ng/mL rise in AMH was associated with 0.09 mg/ dL (95%CI = −0.14 to −0.03; p = 0.002) decrease before and 0.08 mg/dL (95%CI = −0.13 to −0.02; p = 0.004) decrease in CRP after adjusting for potential confounders. Similarly, men in the highest quartile of AMH had significantly lower CRP compared to those in the lowest quartile (unadjusted difference = −0.19 mg/dL; 95%CI = −0.31 to −0.06; p = 0.006, adjusted difference = −0.16 mg/dL; 95%CI = −0.3 to −0.01; p = 0.035). We found an independent, robust, and inverse association between CRP and AMH in men. Effect of AMH on mortality may be through amelioration of inflammation. Anti-mullerian hormone (AMH), is a glycoprotein belonging to the transforming growth factor-beta (TGF-β) superfamily. It is highly expressed in male fetal testis where it is responsible for regression of the mullerian duct. AMH remains elevated until puberty in men and rapidly declines during transition to the adulthood 1,2. While the role of the persistence of AMH during adulthood is unclear, the presence of AMH-specific receptor (AMHRII) in several organs (such as adrenal gland, liver, lung, skeletal muscle, and spleen) suggests that AMH may play a role during adult life beyond the development of reproductive system 3. In fact, epidemiological studies have demonstrated that serum AMH levels were inversely associated with cardiovascular events in elderly male, with infra-renal aortic diameter, and with all-cause mortality in men 4-6. However, the mechanisms underlying of these associations are not known. Growing body of evidence suggests that inflammation plays a critical role in the initiation and progression of atherosclerosis, chronic pulmonary disease (including COPD), and malignancy 7-9. Several studies have reported that serum c-reactive protein (CRP), an inflammatory biomarker, has the ability to predict cardiovascular disease, lung disease, cancer, and all-cause mortality risk in general population 10,11. In one study, serum AMH levels were negatively associated with in...

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Section: Discussionmentioning

confidence: 99%

Association of Anti-Mullerian Hormone with C-Reactive Protein in Men

Kadariya

Kurbanova

Qayyum

2019

Sci Rep

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“…These enzymes have membrane-bound and soluble forms and are expressed by multiple cell types, including neurons (4, 29) and aortic cells (4,26), which are putative sites for hormonal actions of AMH (18,19,31,32,34). Some of these enzymes are induced in response to pathologies such as vascular injury (17,26,28). Hence, some of the AMH in blood may be in an inactive form, as its function may relate to repair and regeneration rather than to day-to-day regulation of healthy tissues.…”

Section: Discussionmentioning

confidence: 99%

Human blood contains both the uncleaved precursor of anti-Müllerian hormone and a complex of the NH₂- and COOH-terminal peptides

Pankhurst

McLennan

2013

American Journal of Physiology-Endocrinology and Metabolism

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Anti-Müllerian hormone (AMH) in blood is a marker of ovarian status in women and the presence of cryptic testes in babies. Despite this, the molecular form of AMH in blood has not been verified. AMH is synthesized as an inert proprotein precursor (proAMH), which can be cleaved to yield NH2-terminal (AMHN) and COOH-terminal (AMHC) fragments, that can complex noncovalently (AMHN,C). Developing males have 10-fold more AMH than young adults. We report here that human blood is a mixture of inactive proAMH and receptor-binding AMHN,C. The AMH in the blood of boys, men, and premenopausal women was immunoprecipitated using antibodies to the NH2- and COOH-terminal peptides. The precipitated proteins were then analyzed by Western blots, using recombinant proteins as markers. The glycosylation status of AMH was verified using deglycosylating enzymes. The NH2-terminal antibody precipitated a major protein that migrated alongside rhproAMH and was detected by anti-AMHN and anti-AMHC. This antibody also precipitated significant levels of AMHN and AMHC from all participants. Antibodies specific to AMHC precipitated rhAMHC but did not precipitate AMHC from human blood. Hence, all the AMHC in human blood appears to be bound to AMHN. Both AMHN and proAMH were glycosylated, independent of age and sex. In conclusion, boys and young adults have the same form of AMH, with a significant proportion being the inactive precursor. This raises the possibility that the endocrine functions of AMH are partly controlled by its cleavage in the target organ. The presence of proAMH in blood may confound the use of AMH for diagnosis.

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“…This idea has been in abeyance, but has substantial merit as the putative cleavage enzymes are widely expressed (Villeneuve et al 1999, Stawowy et al 2001, Cain et al 2003, Veinot et al 2004, under the influence of various physiological and pathological stimuli (Stawowy et al 2001, Veinot et al 2004, Marchesi et al 2011. Under this circumstance, the AMH N,C in circulation defines a basal level of activation, which can be amplified by the local cleavage of proAMH to AMH N,C .…”

Section: Extra-gonadal Cleavage Of Proamhmentioning

confidence: 99%

“…However, proAMH-cleaving enzymes are found in vascular tissues (Stawowy et al 2001, Veinot et al 2004), and it is therefore possible that proAMH is cleaved to AMH N,C whilst in the circulation. Equally, the cardiovascular system is a putative target for circulating AMH (Appt et al 2012, Yarde et al 2014, and any cleavage by vascular sources may only have a local effect.…”

Section: Extra-gonadal Cleavage Of Proamhmentioning

confidence: 99%

Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions

McLennan¹,

Pankhurst²

2015

Journal of Endocrinology

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Anti-Mü llerian hormone (AMH) is a multi-faceted gonadal cytokine. It is present in all vertebrates with its original function in phylogeny being as a regulator of germ cells in both sexes, and as a prime inducer of the male phenotype. Its ancient functions appear to be broadly conserved in mammals, but with this being obscured by its overt role in triggering the regression of the Mü llerian ducts in male embryos. Sertoli and ovarian follicular cells primarily release AMH as a prohormone (proAMH), which forms a stable complex (AMH N,C ) after cleavage by subtilisin/kexin-type proprotein convertases or serine proteinases. Circulating AMH is a mixture of proAMH and AMH N,C , suggesting that proAMH is activated within the gonads and putatively by its endocrine target-cells. The gonadal expression of the cleavage enzymes is subject to complex regulation, and the preliminary data suggest that this influences the relative proportions of proAMH and AMH N,C in the circulation. AMH shares an intracellular pathway with the bone morphogenetic protein (BMP) and growth differentiation factor (GDF) ligands. AMH is male specific during the initial stage of development, and theoretically should produce male biases throughout the body by adding a male-specific amplification of BMP/GDF signalling. Consistent with this, some of the male biases in neuron number and the non-sexual behaviours of mice are dependent on AMH. After puberty, circulating levels of AMH are similar in men and women. Putatively, the function of AMH in adulthood maybe to add a gonadal influence to BMP/GDF-regulated homeostasis.

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Implications of proprotein Convertase 5 (PC5) in the arterial restenotic process in a porcine model

Cited by 8 publications

References 58 publications

Association of Anti-Mullerian Hormone with C-Reactive Protein in Men

Association of Anti-Mullerian Hormone with C-Reactive Protein in Men

Human blood contains both the uncleaved precursor of anti-Müllerian hormone and a complex of the NH₂- and COOH-terminal peptides

Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions

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Implications of proprotein Convertase 5 (PC5) in the arterial restenotic process in a porcine model

Cited by 8 publications

References 58 publications

Association of Anti-Mullerian Hormone with C-Reactive Protein in Men

Association of Anti-Mullerian Hormone with C-Reactive Protein in Men

Human blood contains both the uncleaved precursor of anti-Müllerian hormone and a complex of the NH2- and COOH-terminal peptides

Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions

Contact Info

Product

Resources

About

Human blood contains both the uncleaved precursor of anti-Müllerian hormone and a complex of the NH₂- and COOH-terminal peptides