Serum From Patients With Severe Heart Failure Downregulates eNOS and Is Proapoptotic

Abstract

Serum from patients with severe CHF downregulates eNOS expression and increases apoptosis. High levels of TNF-alpha likely play a role, but they cannot be the only factor responsible.

Serum From Patients With Acute Coronary Syndromes Displays a Proapoptotic Effect on Human Endothelial Cells

“…22 Briefly, endothelial cells were fixed in cold methanol and then incubated with 50 g/mL propidium iodide (PI) and RNAsi, 0.1% Triton X-100 in sodium citrate 0.1%, pH 7.4. Analysis was performed by means of a Coulter Epics XL-MCL flow cytometer equipped with an argon laser at 488 nm wavelength.…”

“…22 Interestingly, in HF, TNF-␣ activation induces a downregulation of endothelial constitutive nitric oxide synthase (eNOS) and has a causal effect on apoptotic process as incubation with an anti-TNF-␣ antibody with serum significantly reduces its apoptotic activity. 22 On the contrary, serum from patients with ACS without HF has a pro-apoptotic effect, which is independent from proinflammatory cytokine levels and does not downregulate eNOS (0.43Ϯ0.14 in control subjects versus 0.44Ϯ0.21 in patients of group 3 at Western blot analysis; data not shown). We have no clear explanation for this discrepancy that could be related to the different pattern of cytokine elevation in these two different clinical situations: TNF-␣ elevation in HF higher and persistent in comparison to the lower and more transient in ACS.…”

CD34 + and Endothelial Progenitor Cells in Patients With Various Degrees of Congestive Heart Failure

“…In HF, nitric oxide production is diminished, whereas rate of endothelial apoptosis is increased. 7,8 Despite these observations, no data are available regarding the pattern of mobilization of EPCs and CD34 ϩ cells during HF. We aimed to assess levels of circulating CD34 ϩ cells and EPCs in patients with HF and correlate them with the origin and severity of the disease.…”

Activation of the Endothelial Nitric-oxide Synthase by Tumor Necrosis Factor-α

“…First, NO acts by inhibiting key apoptogenic signal transduction events triggered by TNF-␣, including ceramide accumulation and TRADD recruitment to the DISC complex, cytochrome c release, as well as the activity of initiator and effector caspases, both before and after their enzymatic cleavage (13)(14)(15)(17)(18)(19). Second, inhibition of endogenous NOS activity during stimulation with TNF-␣ increases apoptosis induction by the cytokine (18,20,21). A direct link between NOS activity and protection from TNF-␣-induced apoptosis was demonstrated by infection experiments with the inducible isoform of NOS, an enzyme that generates NO continuously (16).…”