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
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
.