M. M. Corsi Romanelli

Why menisci show higher healing rate when repaired during ACL reconstruction? Growth factors release can be the explanation

PurposeHealing rate of meniscus repair is higher when the suture is associated with anterior cruciate ligament reconstruction. A possible explanation can be a different pattern of release of growth factors between anterior cruciate ligament reconstruction and isolated meniscus surgery. Hypothesis of this study is that the concentrations of bFGF, TGF-β and platelet-derived growth factor (PDGF) in joint fluid, immediately after single-bundle anterior cruciate ligament reconstruction and arthroscopic partial meniscectomy, can be different.MethodsTwenty consecutive patients underwent partial medial meniscectomy and twenty consecutive patients underwent single-bundle anterior cruciate ligament reconstruction with hamstring grafts were enrolled in the study. Thirty minutes after the end of the surgical procedure, a sample of joint fluid, as well of venous blood, was collected from all the patients. Concentrations of growth factors were determined by enzyme-linked immunosorbent assay.ResultsThe peripheral blood concentration of TGF-β, bFGF and PDGF was comparable between partial meniscectomy and anterior cruciate ligament reconstruction groups. No differences between the two surgical techniques were also found in term of TGF-β and bFGF joint fluid concentration, whereas joint PDGF concentration of anterior cruciate ligament reconstruction patients was significantly higher than the one found in partial meniscectomy patients.ConclusionsA significant growth factors release was detected in the knee joint during arthroscopic surgery. PDGF concentration was significantly higher in anterior cruciate ligament reconstructed knee than in the meniscectomy group. PDGF can play an important role enhancing the healing response of meniscus suture and can be one of the biological reasons of the higher meniscal healing rate in anterior cruciate ligament reconstructed knee.

Epicardial adipose tissue inflammation is related to vitamin D deficiency in patients affected by coronary artery disease

BACKGROUND AND AIMS Alterations in epicardial adipose tissue (EAT) biology (i.e. increased fat thickness and inflammation) have been described in coronary artery disease (CAD) patients. In addition to its classic role in the regulation of calcium-phosphate homeostasis, vitamin D may exert immune-regulatory and anti-inflammatory effects. Whether EAT inflammation may be linked to vitamin D deficiency is still unknown. In the present study we evaluated plasma 25-hydroxycholecalciferol (25OHD) level in CAD patients and its relationship with EAT ability to locally metabolize vitamin D, EAT expression of inflammation-related molecules and EAT thickness. METHODS AND RESULTS Plasma 25OHD level was quantified by an immunoluminometric assay. EAT expression of inflammation-related molecules (MCP-1, PTX3, TNFα, IL-6, adiponectin), vitamin D receptor (VDR), CYP27B1 (25OHD-activating enzyme) and CYP24A1 (1,25-dihydroxycholecalciferol-metabolizing enzyme) was performed by microarray. EAT thickness was quantified by echocardiography. Median plasma 25OHD level was 10.85 ng/mL and 83% of CAD patients displayed 25OHD level below 20 ng/mL. At decreasing plasma 25OHD concentration, we observed a down-regulation in CYP27B1 and CYP24A1 level and an increased expression of VDR and pro-inflammatory cytokines (MCP-1, PTX3, TNFα, IL-6) at EAT level. No correlation was observed between plasma 25OHD level and EAT thickness. CONCLUSION Our data suggest an increased activation of inflammatory pathways at EAT level possibly related to systemic and local vitamin D deficiency in CAD patients. Whether maintaining an optimal vitamin D status may be helpful to reduce EAT inflammation and to prevent CAD and its progression needs further investigation.

Epicardial adipocyte hypertrophy: Association with M1-polarization and toll-like receptor pathways in coronary artery disease patients.

BACKGROUND AND AIMS In coronary artery disease (CAD) epicardial adipose tissue (EAT) shows an elevated inflammatory infiltrate. Toll-like receptors (TLRs) are important mediators of adipose tissue inflammation and they are able to recognize endogenous products released by damaged cells. Because adipocyte death may be driven by hypertrophy, our aim was to investigate in CAD and non-CAD patients the association between EAT adipocyte size, macrophage infiltration/polarization and TLR-2 and TLR-4 expression. METHODS AND RESULTS EAT biopsies were collected from CAD and non-CAD patients. The adipocyte size was determined by morphometric analysis. Microarray technology was used for gene expression analysis; macrophage phenotype and TLRs expression were analyzed by immunofluorescence and immunohistochemical techniques. Inflammatory mediator levels were determined by immunoassays. EAT adipocytes were larger in CAD than non-CAD patients and do not express perilipin A, a marker of lipid droplet integrity. In CAD, EAT is more infiltrated by CD68-positive cells which are polarized toward an M1 state (CD11c positive) and presents an increased pro-inflammatory profile. Both TLR-2 and TLR-4 expression is higher in EAT from CAD and observed on all the CD68-positive cells. CONCLUSIONS Our findings suggested that EAT hypertrophy in CAD promotes adipocyte degeneration and drives local inflammation through increased infiltration of macrophages which are mainly polarized towards an M1 state and express both TLR-2 and TLR-4.

Levels of L-arginine and L-citrulline in patients with erectile dysfunction of different etiology

Nitric oxide is a physiologic signal essential to penile erection. l‐citrulline (l‐Cit) is converted into l‐arginine (l‐Arg), the precursor from which nitric oxide is generated. The level of l‐Arg and l‐Cit in the field of male sexual function remains relatively underexplored. The aim of the study was to evaluate the level of serum l‐Arg and of l‐Cit in a group of patients with erectile dysfunction. Diagnosis and severity of erectile dysfunction was based on the IIEF‐5 and its etiology was classified as arteriogenic (A‐ED), borderline (BL‐ED), and non‐arteriogenic (NA‐ED) with penile echo‐color‐Doppler in basal condition and after intracaversous injection of prostaglandin E1. Serum l‐Arg and l‐Cit concentrations were measured by a cation‐exchange chromatography system. l‐Arg and l‐Cit levels of men with A‐ED were compared with those of male with BL‐ED and NA‐ED. Median level of l‐Arg and l‐Cit in 122 erectile dysfunction patients (41 A‐ED, 23 ED‐BL, 58 NA‐ED) was 82.7 and 35.4 μmol/L, respectively. l‐Arg and l‐Cit levels in control patients were not significantly different (p = 0.233 and p = 0.561, respectively) than in total erectile dysfunction patients. l‐Arg and l‐Cit levels in control patients were significantly higher (p < 0.001 and p < 0.018, respectively) than in A‐ED patients, but no difference (p > 0.50) was observed in controls and in both BL‐ED and NA‐ED patients. Patients with severe/complete‐erectile dysfunction (IIEF‐5 < 10) had l‐Arg or l‐Cit level significantly lower (−17%, p < 0.03; −13%, p < 0.04) and were more frequent (p < 0.01 and p < 0.04) under the respective median level (82.7 and 35.4 μmol/L) than those with mild‐erectile dysfunction (IIEF‐5 = 16–20). l‐Arg and l‐Cit levels in A‐ED were significantly lower (p < 0.007 and p < 0.001, respectively) than in NA‐ED patients. Penile echo‐color‐Doppler revealed that A‐ED (peak systolic velocity ≤ 25 cm/sec) was more frequent in men with l‐Arg under 82.7 μmol/L or l‐Cit under 35.4 μmol/L and in the same population, the median peak systolic velocity values were lower in l‐Arg deficient (29 vs. 35; p < 0.04) and also in l‐Cit deficient (31 vs. 33, p > 0.3) but without reaching the statistical significance. Our study shows that a significant proportion of erectile dysfunction patients have low l‐Arg or l‐Cit level and that this condition is more frequent in patients with arteriogenic etiology. Low levels of these nitric oxide synthase substrates might increase the erectile dysfunction risk by reducing the concentration of nitric oxide.