Exploring the microvascular impact of red blood cell transfusion in intensive care unit patients.

Background: Red blood cell (RBC) transfusion is a common treatment for hospitalized patients. However, the effects of RBC transfusion on microvascular function remain controversial.

Methods: In a medical ICU in a tertiary teaching hospital, we prospectively included anemic patients requiring RBC transfusion.

Intravascular hemolysis activates complement via cell-free heme and heme-loaded microvesicles.

In hemolytic diseases, such as sickle cell disease (SCD), intravascular hemolysis results in the release of hemoglobin, heme, and heme-loaded membrane microvesicles in the bloodstream. Intravascular hemolysis is thus associated with inflammation and organ injury. Complement system can be activated by heme in vitro.

Massive release of extracellular vesicles from cancer cells after photodynamic treatment or chemotherapy.

Photodynamic therapy is an emerging cancer treatment that is particularly adapted for localized malignant tumor. The phototherapeutic agent is generally injected in the bloodstream and circulates in the whole organism as a chemotherapeutic agent, but needs light triggering to induce localized therapeutic effects. We found that one of the responses of in vitro and in vivo cancer cells to photodynamic therapy was a massive production and emission of extracellular vesicles (EVs): only 1 hour after the photo-activation, thousands of vesicles per cell were emitted in the extracellular medium.

Erythrocyte microparticles can induce kidney vaso-occlusions in a murine model of sickle cell disease.

Patients with sickle cell disease suffer from painful crises associated with disseminated vaso-occlusions, increased circulating erythrocyte microparticles (MPs), and thrombospondin-1 (TSP1). MPs are submicron membrane vesicles shed by compromised or activated cells. We hypothesized that TSP1 mediates MP shedding and participates in vaso-occlusions.

C/EBP homologous protein-10 (CHOP-10) limits postnatal neovascularization through control of endothelial nitric oxide synthase gene expression.

Background: C/EBP homologous protein-10 (CHOP-10) is a novel developmentally regulated nuclear protein that emerges as a critical transcriptional integrator among pathways regulating differentiation, proliferation, and survival. In the present study, we analyzed the role of CHOP-10 in postnatal neovascularization.

Methods And Results: Ischemia was induced by right femoral artery ligation in wild-type and CHOP-10(-/-) mice.

Cardiomyocyte overexpression of neuronal nitric oxide synthase delays transition toward heart failure in response to pressure overload by preserving calcium cycling.

Background: Defects in cardiomyocyte Ca(2+) cycling are a signature feature of heart failure (HF) that occurs in response to sustained hemodynamic overload, and they largely account for contractile dysfunction. Neuronal nitric oxide synthase (NOS1) influences myocyte excitation-contraction coupling through modulation of Ca(2+) cycling, but the potential relevance of this in HF is unknown.

Methods And Results: We generated a transgenic mouse with conditional, cardiomyocyte-specific NOS1 overexpression (double-transgenic [DT]) and studied cardiac remodeling, myocardial Ca(2+) handling, and contractility in DT and control mice subjected to transverse aortic constriction (TAC).

Evidence of a role for lactadherin in Alzheimer's disease.

Lactadherin is a secreted extracellular matrix protein expressed in phagocytes and contributes to the removal of apoptotic cells. We examined lactadherin expression in brain sections of patients with or without Alzheimer's disease and studied its role in the phagocytosis of amyloid beta-peptide (Abeta). Cells involved in Alzheimer's disease, including vascular smooth muscle cells, astrocytes, and microglia, showed a time-related increase in lactadherin production in culture.

Association of annexin A5 with Na+/Ca2+ exchanger and caveolin-3 in non-failing and failing human heart.

Annexin A5 is a Ca2+ dependent phosphatidylserine binding protein mainly located in the T-tubules and sarcolemma of cardiomyocytes. Our objectives were to determine whether annexin A5 was associated with various protein(s) and whether such an association was modified in failing (F) hearts. The association between annexin A5 and the cardiac Na+/Ca2+ exchanger (NCX) was demonstrated by immunohistofluorescence, annexin A5-biotin overlay and co-immunoprecipitations (IPs) performed with microsomal preparations (MPs) from non-failing (NF) (n = 8) and F (dilated cardiomyopathy, n = 7) human hearts.

Externalization of endogenous annexin A5 participates in apoptosis of rat cardiomyocytes.

Objective: Annexins are Ca(2+)-dependent phospholipid binding proteins. Externalized annexin A5 has been recently suggested to have a proapoptotic effect. Our aim was to determine whether annexin A5, which is intracellular in cardiomyocytes, could be translocated and/or externalized and play a role during the apoptotic process.