Matrix Metalloproteinase‐2 Activity is Associated with Divergent Regulation of Calponin‐1 in Conductance and Resistance Arteries in Hypertension‐induced Early Vascular Dysfunction and Remodelling

Matrix metalloproteinase (MMP)‐2 participates in hypertension‐induced maladaptive vascular remodelling by degrading extra‐ and intracellular proteins. The consequent extracellular matrix rearrangement and phenotype switch of vascular smooth muscle cells (VSMCs) lead to increased cellular migration and proliferation. As calponin‐1 degradation by MMP‐2 may lead to VSMC proliferation during hypertension, the hypothesis of this study is that increased MMP‐2 activity contributes to early hypertension‐induced maladaptive remodelling in conductance and resistance arteries via regulation of calponin‐1. The main objective was to analyse whether MMP‐2 exerts similar effects on the structure and function of the resistance and conductance arteries during early hypertension. Two‐kidney, one‐clip (2K‐1C) hypertensive male rats and corresponding controls were treated with doxycycline (30 mg/kg/day) or water until reaching one week of hypertension. Systolic blood pressure was increased in 2K‐1C rats, and doxycycline did not reduce it. Aortas and mesenteric arteries were analysed. MMP‐2 activity and expression were increased in both arteries, and doxycycline reduced it. Significant hypertrophic remodelling and VSMC proliferation were observed in aortas but not in mesenteric arteries of 2K‐1C rats. The contractility of mesenteric arteries to phenylephrine was increased in 2K‐1C rats, and doxycycline prevented this alteration. The potency of phenylephrine to contract aortas of 2K‐1C rats was increased, and doxycycline decreased it. Whereas calponin‐1 expression was increased in 2K‐1C mesenteric arteries, calponin‐1 was reduced in aortas. Doxycycline treatment reverted changes in calponin‐1 expression. MMP‐2 contributes to hypertrophic remodelling in aortas by decreasing calponin‐1 levels, which may result in VSMC proliferation. On the other hand, MMP‐2‐dependent increased calponin‐1 in mesenteric arteries may contribute to vascular hypercontractility in 2K‐1C rats. Divergent regulation of calponin‐1 by MMP‐2 may be an important mechanism that leads to maladaptive vascular effects in hypertension.     

Effects of resistance training of moderate intensity on heart rate variability,body composition,and muscle strength in healthy elderly women

Purpose

The practice of resistance training is recommended as non-pharmacological strategy during aging. In this study, we propose training composed of exercises, leg 180° press, seated row, leg curl, bench press, abduction machine, push down, adduction machine, and curl biceps. Accordingly, this study aimed to determine the effects of dynamic resistance training on autonomic response, muscle strength, and body composition of elderly women without comorbidities.

Methods

Twenty-six healthy older women (65 ± 3 years) were randomly divided into two groups. The Control Group (CG) consisted of 13 subjects not engaged in any physical exercise, while the Training Group (GT) (n = 13) performed 8 strength training exercises with 3 sets of 8 maximum repetitions. Heart rate variability, body composition, and muscle strength were assessed before and after the 12 weeks in both groups.

Results

No significant difference was found in body composition, muscle strength, and heart rate variability between CG and TG before (baseline) 12 weeks of training. Significant differences between pre- and post-training moments were found only in training group. In this sense, results demonstrated improvement (p < 0.05) in body fat mass (23.0 ± 1.2 vs. 20.0 ± 1.1 kg), fat-free mass (38.0 ± 1.5 vs. 42.0 ± 1.4 kg), strength of upper (17.8 ± 1.0 vs. 22.2 ± 1.1 kgf) and lower limbs (27.1 ± 2.4 vs. 34.1 ± 2.5 kgf), and in time and frequency domain measures of heart rate variability, highlighting the indices LF/HF (1.2 ± 0.4 vs. 0.7 ± 0.1).

Conclusions

The dynamic resistance training protocol presented in this study may be regarded as an effective approach to prevent cardiovascular morbidity and mortality in elderly women.

     

Histocompatibility class I and II antigens in extensive kindred with Sneddon's syndrome and related hypercoagulation disorders

We have studied the relationship between the histocompatibility class I and II antigens and Sneddon's syndrome (SS) in a Spanish patient with SS and her relatives (13 available members of an extensive 3-generation pedigree with diverse autoimmune hypercoagulation abnormalities). The patient and her father were diagnosed with a primary antiphospholipid antibody syndrome and were HLA-A30-B13-Bw6. In addition, a HLA-Bw6-DQ1 association was present in all the members of this kindred. These data suggest that the combination of the histocompatibility class I and II antigens in this family may be a marker for predisposition to SS.     

The role of macrophage migration inhibitory factor in the cascade of events leading to reperfusion-induced inflammatory injury and lethality

Ischemia and reperfusion (I/R) injury is associated with a systemic inflammatory response, characterized by intense tumor necrosis factor (TNF)-alpha production and TNF-alpha-dependent tissue injury. Macrophage migration inhibitory factor (MIF) is a potent proinflammatory cytokine that may induce TNF-alpha release and play an important role in innate immune and inflammatory responses. The aim of this work was to assess whether MIF was involved the inflammatory cascade and injury that follows intestinal I/R. To this end, wild-type (WT) and MIF-deficient (MIF(-/-)) mice underwent 60 minutes of ischemia followed by 60 minutes of reperfusion, after which they were culled for the assessment of inflammatory parameters. I/R was accompanied by an increase in circulating levels of MIF and an increase of vascular permeability, hemorrhage, and production of TNF-alpha in the intestine and lungs. The latter parameters were markedly suppressed in reperfused MIF(-/-) mice, and this was associated with decreased lethality (80% in WT versus 20% in MIF(-/-) mice). Interestingly, the reperfusion-associated neutrophil accumulation in the intestine and lungs was similar in WT and MIF(-/-) mice. Leukocytes isolated from lungs of MIF(-/-) mice were less activated, as assessed by their response to zymosan in a luminol-enhanced chemiluminescence assay. In conclusion, our results suggest that MIF plays an important role in the cascade of events leading to TNF-alpha production and reperfusion-induced tissue injury and lethality in mice.     

Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides

Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches.     

Peri-implant bone regeneration with calcium sulfate: a light and transmission electron microscopy case report

BACKGROUND: Calcium sulfate is a simple, biocompatible material with a very long, safe clinical history in several different fields of medicine. It is a rapidly resorbing material that leaves behind calcium phosphate lattice, which promotes bone regeneration. OBJECTIVE: The aim of this study was a histological and ultrastructural evaluation of the tissues in a peri-implant site regenerated with calcium sulfate. MATERIALS AND METHODS: The specimens were processed for observation under light and transmission electron microscopes. RESULTS: In light microscopy, trabecular bone was present. No remnants of calcium sulfate were present. Transmission electron microscopy showed, in the areas of the interface with the implant surface, features of mature bone with many osteocytes. An amorphous layer and/or osteoid seam separated this mature bone from the metal surface. CONCLUSION: The results confirm the high biocompatibility and rapid resorption of calcium sulfate.     

Human peri-implant bone response to turned and oxidized titanium implants inserted and retrieved after 2 months

PURPOSE: The aim of this study was to evaluate the influence of oxidized surface on bone-to-implant contact percentage (BIC%) as well as the bone density within the threads area (BD%) in human bone after 2 months of unloaded healing. MATERIALS: Seven subjects (mean age 45.57 +/- 10.45 years) received 2 micro-implants each during conventional implant surgery in the posterior maxilla. The implants that presented turned and oxidized surfaces served as control and test, respectively. After the healing period, the implants and the surrounding tissue were removed and prepared for ground sectioning and analysis. RESULTS: Two turned implants were found to be clinically unstable at the time of retrieval. Histometric evaluation showed that the mean of BIC% was 17.40 +/- 14.16% and 32.19 +/- 15.68% to turned and oxidized surfaces, respectively. The BD% was 22.13 +/- 19.06% for turned surface and 50.40 +/- 18.35% for oxidized surface. CONCLUSION: The histologic data from this preliminary study suggest that the oxidized micro-implants surface presented better mean values of BIC% and BD% than turned micro-implants after a short healing time.