Circulating Microparticles Carry a Functional Endothelial Nitric Oxide Synthase That Is Decreased in Patients With Endothelial Dysfunction

نویسندگان

  • Patrick Horn
  • Miriam Margherita Cortese‐Krott
  • Nicolas Amabile
  • Claas Hundsdörfer
  • Klaus‐Dietrich Kröncke
  • Malte Kelm
  • Christian Heiss
چکیده

BACKGROUND Microparticles (MPs) are circulating membrane particles of less than a micrometer in diameter shed from endothelial and blood cells. Recent literature suggests that MPs are not just functionally inert cell debris but may possess biological functions and mediate the communication between vascular cells. As a significant proportion of MPs originate from platelets and endothelial cells, we hypothesized that MPs may harbor functional enzymes including an endothelial NO synthase (eNOS). METHODS AND RESULTS Using immunoprecipitation and Western blot analysis, we found that human circulating MPs carry an eNOS. Ca(2+) and l-arginine-dependent NOS activity of crude enzyme extract from MPs was determined by measuring the conversion of [(3)H]-L-arginine to [(3)H]-citrulline and NOS-dependent nitrite production. NOS-dependent NO production in intact MPs was assessed by the NO-specific fluorescent probe MNIP-Cu. In patients with cardiovascular disease, endothelial dysfunction was associated with an increase in the total number of circulating MPs as well as a significant decrease in the expression and activity of eNOS in MPs. No difference in reactive oxygen species was noted in MPs isolated from either group. CONCLUSIONS Our data further support the concept that circulating MPs may not only retain phenotypic markers but also preserve the functionality of enzymes of the cells they originate from, including eNOS.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction.

BACKGROUND Shed membrane microparticles circulate in the peripheral blood of nonischemic (NI) patients and patients with myocardial infarction (MI). We investigated whether or not these microparticles would affect endothelium-dependent responses. METHODS AND RESULTS Rat aortic rings with endothelium were exposed for 24 hours to circulating microparticles isolated from 7 patients with NI syndr...

متن کامل

Association between T-786C polymorphism of endothelial nitric oxide synthase gene and level of the vessel dilation factor in patients with coronary artery disease

Various polymorphisms on endothelial nitric oxide synthase (eNOs) gene cause reduced production of NO, the endothelial relaxing factor, and may accelerate the process of atherosclerosis. The study designed to investigate the frequency of T-786C polymorphism of the eNOs gene in patients suffering from coronary artery disease (CAD) in north-west of Iran. One hundred twenty subjects including 60 p...

متن کامل

P-235: No Association of Endothelial Nitric Oxide Synthase (eNOS) -786T/C Polymorphism with Unexplained Recurrent Abortion in Iranian Women

Background: This is a case-control study to determine the relationship between endothelial nitric oxide synthase (eNOS) gene -786T/C polymorphism in women with unexplaiend recurrent abortion in comparison with healty women.Materials and Methods: 95 women with history of at least 2 unexplaiend recurrent abortion in the reproductive age range 20-35 years as patients group and 95 healty women (age...

متن کامل

EXPRESSION OF INDUCIBLE NITRIC OXIDE SYNTHASE GENE (iNOS) STIMULATED BY HYDROGEN PEROXIDE IN HUMAN ENDOTHELIAL CELLS

Inducible nitric oxide synthase (iNOS) gene expresses a calcium calmudolin-independent enzyme which can catalyse NO production from L-arginine. The induction of iNOS activity has been demonstrated in a wide variety of cell types under stimulation with cytokines and lipopoly saccharide (LPS). Previous studies indicated that all nitric oxide synthases (NOS) activated in human umbilical vein endot...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 2  شماره 

صفحات  -

تاریخ انتشار 2012