Cardiomyocytes bind and activate native human prorenin - Role of soluble mannose 6-phosphate receptors

Citation
Jj. Saris et al., Cardiomyocytes bind and activate native human prorenin - Role of soluble mannose 6-phosphate receptors, HYPERTENSIO, 37(2), 2001, pp. 710-715
Citations number
28
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
HYPERTENSION
ISSN journal
0194911X → ACNP
Volume
37
Issue
2
Year of publication
2001
Part
2
Supplement
S
Pages
710 - 715
Database
ISI
SICI code
0194-911X(200102)37:2<710:CBAANH>2.0.ZU;2-1
Abstract
Cardiomyocytes bind, internalize, and activate recombinant human prorenin t hrough mannose 6-phosphate/insulin-like growth factor II (M6P/IGFII) recept ors. To investigate whether this also applies to native human prorenin, neo natal rat myocytes were incubated for 4 hours at 37 degreesC with various p rorenin-containing human body fluids. Uptake and activation by M6P/IGFII re ceptors were observed for plasma prorenin from subjects with renal artery s tenosis and/or hypertension and for follicular fluid prorenin. The total am ount of cellular renin and prorenin (expressed as percentage of the levels of renin and prorenin in the medium) after 4 hours of incubation was 4 to 1 0 times lower than after incubation with recombinant human prorenin. Althou gh plasma contains alkaline phosphatases capable of inactivating the M6P la bel as well as soluble M6P/IGFII receptors that block prorenin binding in a competitive manner and proteins (eg, insulin, IGFII) that increase the num ber of cell-surface M6P/IGFII receptors, these factors were not responsible for the modest uptake of native human prorenin. Uptake did not occur durin g incubation of myocytes with plasma prorenin from anephric subjects or wit h amniotic fluid prorenin, and this was not due to the presence of excessiv ely high levels of M6P/IGFII receptors and/or phosphatase activity in these fluids. in conclusion, myocytes are capable of binding, internalizing, and activating native human prorenin of renal and ovarian origin through M6P/I GFII receptors. Differences in prorenin glycosylation and/or phosphorylatio n as well as the concentration of soluble M6P/IGFII receptors and growth fa ctors affecting cell-surface M6P/IGFlI receptor density determine the amoun t of prorenin entering the heart and thus cardiac angiotensin II production .