Erythropoietin Receptor Signaling Mitigates Renal Dysfunction-Associated Heart Failure by Mechanisms Unrelated to Relief of Anemia

ObjectivesWe examined the effect of asialoerythropoietin (asialoEPO), a nonerythrogenic derivative of erythropoietin (EPO), on renal dysfunction-associated heart failure.BackgroundAlthough EPO is known to exert beneficial effects on cardiac function, the clinical benefits in patients with chronic kidney disease are controversial. It remains to be addressed whether previously reported outcomes were the result of relief of the anemia, adverse effects of EPO, or direct cardiovascular effects.MethodsMice underwent 5/6 nephrectomy to cause renal dysfunction. Eight weeks later, when renal dysfunction was established, anemia and cardiac dysfunction and remodeling were apparent. Mice were then assigned to receive saline (control), recombinant human erythropoietin (rhEPO) at 5,000 IU (714 pmol)/kg, or asialoEPO at 714 pmol/kg, twice/week for 4 weeks.ResultsAlthough only rhEPO relieved the nephrectomy-induced anemia, both rhEPO and asialoEPO significantly and similarly mitigated left ventricular dilation and dysfunction. The hearts of rhEPO- or asialoEPO-treated mice showed less hypertrophy, reflecting decreases in cardiomyocyte hypertrophy and degenerative subcellular changes, as well as significant attenuation of fibrosis, leukocyte infiltration, and oxidative deoxyribonucleic acid damage. These phenotypes were accompanied by restored expression of GATA-4, sarcomeric proteins, and vascular endothelial growth factor and decreased inflammatory cytokines and lipid peroxidation. Finally, myocardial activation was observed of extracellular signal-regulated protein kinase and signal transducer and activator of transcription pathways in the treated mice.ConclusionsEPO receptor signaling exerts direct cardioprotection in an animal model of renal dysfunction-associated heart failure, probably by mitigating degenerative, pro-fibrosis, inflammatory, and oxidative processes but not through relief of anemia

Deletion of caveolin scaffolding domain alters cancer cell migration

Caveolin-1 (Cav-1) is an integral membrane protein that plays an important role in proliferative and terminally differentiated cells. As a structural component of Caveolae, Cav-1 interacts with signaling molecules via a caveolin scaffolding domain (CSD) regulating cell signaling. Recent reports have shown that Cav-1 is a negative regulator in tumor metastasis. Therefore, we hypothesize that Cav-1 inhibits cell migration through its CSD. HeLa cells were engineered to overexpress Cav-1 (Cav-1 OE), Cav-1 without a functional CSD (∆CSD), or enhanced green fluorescent protein (EGFP) as a control. HeLa cell migration was suppressed in Cav-1 OE cells while ∆CSD showed increased migration, which corresponded to a decrease in the tight junction protein, zonula occludens (ZO-1). The migration phenotype was confirmed in multiple cancer cell lines. Phosphorylated STAT-3 was decreased in Cav-1 OE cells compared to control and ∆CSD cells; reducing STAT-3 expression alone decreased cell migration. ∆CSD blunted HeLa proliferation by increasing the number of cells in the G2/M phase of the cell cycle. Overexpressing the CSD peptide alone suppressed HeLa cell migration and inhibited pSTAT3. These findings suggest that Cav-1 CSD may be critical in controlling the dynamic phenotype of cancer cells by facilitating the interaction of specific signal transduction pathways, regulating STAT3 and participating in a G2/M checkpoint. Modulating the CSD and targeting specific proteins may offer potential new therapies in the treatment of cancer metastasis

Feasibility and safety of jailed-pressure wire technique using durable optical fiber pressure wire for intervention of coronary bifurcation lesions

Objectives: The objective was to evaluate the safety, feasibility, and accuracy of the jailed-pressure wire technique using a durable optical fiber-based pressure wire with high-pressure dilatation using a non-compliant balloon after main vessel stenting. Background: Fractional flow reserve (FFR) information can help interventionists determine whether they should treat a jailed-side branch (SB). However, re-crossing a pressure wire into a jailed-SB is sometimes technically difficult. Methods: Fifty-one consecutive lesions from 48 patients who underwent the jailed-pressure wire technique were retrospectively investigated. The primary endpoint was complication rate and secondary endpoints included success rate of FFR measurement, incidence of wire disruption, and final drift rate. The usability of FFR for percutaneous coronary intervention of coronary bifurcation lesion was also evaluated. Results: Median age of the patients was 69 years and 80.4% were men. The most frequent underlying disease was stable angina (70.6%) and 68.6% were type B2 lesions. Our main findings were: the procedure was performed successfully in all cases without any complications or wire disruption, FFR could be measured without significant final drift in 95.9% of cases, and FFR measurements helped interventionists determine whether to perform a final kissing balloon dilatation in 49.0% cases. Conclusions: The jailed-pressure wire technique using a durable optical fiber-based pressure wire with high-pressure post-dilatation maneuver was safe, feasible, and accurate

Feasibility and safety of jailed‐pressure wire technique using durable optical fiber pressure wire for intervention of coronary bifurcation lesions

Objectives: The objective was to evaluate the safety, feasibility, and accuracy of the jailed-pressure wire technique using a durable optical fiber-based pressure wire with high-pressure dilatation using a non-compliant balloon after main vessel stenting. Background: Fractional flow reserve (FFR) information can help interventionists determine whether they should treat a jailed-side branch (SB). However, re-crossing a pressure wire into a jailed-SB is sometimes technically difficult. Methods: Fifty-one consecutive lesions from 48 patients who underwent the jailed-pressure wire technique were retrospectively investigated. The primary endpoint was complication rate and secondary endpoints included success rate of FFR measurement, incidence of wire disruption, and final drift rate. The usability of FFR for percutaneous coronary intervention of coronary bifurcation lesion was also evaluated. Results: Median age of the patients was 69 years and 80.4% were men. The most frequent underlying disease was stable angina (70.6%) and 68.6% were type B2 lesions. Our main findings were: the procedure was performed successfully in all cases without any complications or wire disruption, FFR could be measured without significant final drift in 95.9% of cases, and FFR measurements helped interventionists determine whether to perform a final kissing balloon dilatation in 49.0% cases. Conclusions: The jailed-pressure wire technique using a durable optical fiber-based pressure wire with high-pressure post-dilatation maneuver was safe, feasible, and accurate