Shock Absorption Capacity of High-Performance Polymers for Dental Implant-Supported Restorations: In Vitro Study.

BACKGROUND: Restorative materials might significantly affect load transmission in peri-implant bone. The aim of the present study is to evaluate the shock absorption capacity of two different polymeric materials to be used for implant-supported prostheses. METHODS: A masticatory robot was used to compare the shock absorption capacity of veneered and non-veneered polyetherketoneketone (PEKK), Pekkton®ivory (Cendres+Mètaux), and the glass fiber-reinforced composite (GFRC), TRINIATM (Bicon). Five identical sample crowns for each of the three groups were tested. Forces transmitted at the simulated peri-implant bone were recorded and statistically analyzed. RESULTS: The statistical analysis of forces transmitted at the simulated dental implant revealed significant differences between the materials tested and between these materials and zirconia, glass ceramic, composite resin, and acrylic resin. Only differences between PEKK and veneered PEKK and between PEKK and one of the previously tested composite resins were not statistically significant. PEKK samples demonstrated significantly greater shock absorption capacity compared to GFRC. CONCLUSIONS: PEKK revealed optimal shock absorption capacity. Further studies are needed to evaluate its efficacy in the case of long-span prostheses with reduced prosthetic volume.

Antimicrobial Activity of Glycine Air Polishing: A Clinical Split- Mouth Study on Full-Arch Implant-Supported Rehabilitations.

PURPOSE: To investigate the possible antimicrobial activity of glycine air polishing by comparing peri-implant microbiota before and after treatment. MATERIALS AND METHODS: A total of 15 patients who received implant-supported full-arch fixed rehabilitations were included. After prosthesis removal (T0), Plaque Index (PI), probing depth (PD), and bleeding on probing (BOP) were recorded. In each hemiarch, the implant with the highest PD score was selected for microbiologic sample collection from the peri-implant sulcus (T0). All patients received two different hygienic protocols (randomly administered, one per each hemiarch): glycine air-polishing (G) and cleansing with cotton pellets soaked in saline (C). At 7 days (T1) and 3 months (T2) after the intervention, PI and BOP were recorded, and new microbiologic samples were taken. Traditional polymerase chain reaction (PCR) and quantitative PCR real-time were employed for microbiologic analysis to investigate how the presence of different bacterial species varied according to the hygienic treatment performed. RESULTS: Treatment G provided a significantly higher PI score reduction around implants compared to treatment C (P = .015). No statistical difference was found in the microbial population around G and C implant sites, with Tannerella forsythia being the most commonly detected bacterial species in both G and C groups. No statistical differences were found between the antimicrobial activity of treatments C and G. CONCLUSIONS: Glycine powder air polishing is a valid method for professional hygienic care of implants and was more effective in PI reduction compared to the control treatment. However, its antimicrobial efficacy cannot be confirmed by the outcomes of the present study.

Biomarkers from Peri-Implant Crevicular Fluid (PICF) as Predictors of Peri-Implant Bone Loss: A Systematic Review.

The aim of the present systematic review is to summarize current knowledge regarding the analysis of biomarkers extracted from peri-implant crevicular fluid (PICF) as predictors of peri-implant bone loss (BL). An electronic search was conducted on three databases, PubMed/MEDLINE, Cochrane Library, and Google Scholar, to find clinical trials published until 1 December 2022 suitable to answer the following focused question: in patients with dental implants, are biomarkers harvested from PICF predictive of peri-implant BL? The initial search yielded a total of 158 entries. After a full-text review and application of the eligibility criteria, the final selection consisted of nine articles. The risk of bias in included studies was assessed using the Joanna Briggs Institute Critical Appraisal tools (JBI). According to the present systematic review, some inflammatory biomarkers harvested from PICF (collagenase-2, collagenase-3, ALP, EA, gelatinase b, NTx, procalcitonin, IL-1ß, and several miRNAs) seem to be correlated with peri-implant BL and may assist in the early diagnosis of pathological BL, that characterizes peri-implantitis. MiRNA expression demonstrated a predictive potential of peri-implant BL that could be useful for host-targeted preventive and therapeutic purposes. PICF sampling may represent a promising, noninvasive, and repeatable form of liquid biopsy in implant dentistry.

One-stage versus two-stage technique using two splinted extra-short implants: A multicentric split-mouth study with a one-year follow-up.

OBJECTIVE: To compare the clinical outcomes of extra-short implants (≤6.5 mm) inserted with one-stage versus two-stage technique in adjacent sites of the upper or lower jaw. MATERIALS AND METHODS: In this split-mouth multicenter study, implants were randomly divided into two groups according to the healing phase: two-stage and one-stage technique. Primary outcome measures were implant survival, implant success, and prosthodontic complications. Secondary outcome measurements were: implant stability quotient (ISQ) collected at surgery time (T0), and after 3 (T3) and 12 (T12) months, marginal bone level (MBL) evaluated at T0, T3, T6, and T12, marginal bone loss evaluated at T6 and T12, plaque index (PI), probing depth (PD), bleeding on probing (BoP) evaluated at T3, T6, and T12. Significances of differences between groups were tested by linear mixed model with random intercept. RESULTS: Nineteen patients (8 males and 11 females) were included. A total of 38 implants were inserted. At T12 implant cumulative survival and implant success rate were 100% in both groups. No statistically significant differences were recorded for any of the analyzed parameters between the two groups at any time point. ISQ values were similar at T0 (two-stage: mean 67.53 ± SD 19.47; one-stage: mean 66.53 ± 19.07 p = 0.8738) and increased in both groups at the 12-month follow-up appointment (two-stage: 81.1 ± 7.04; one-stage: 81.39 ± 0.9266). MBL values were similar in the two groups at any time point. At T12 marginal bone loss was 0.46 ± 0.41 (two-stage) and 0.45 ± 0.38 (one-stage) mm (p = 0.9417), while mean PD was 2.7 ± 0.85 (two-stage) and 2.69 ± 0.89 (one-stage) mm. CONCLUSIONS: Within the limits of the present short-term report, extra-short implants demonstrated optimal clinical outcomes using the one-stage technique, without statistically significant differences compared with the traditional two-stage approach.

Efficacy of air-polishing devices without removal of implant-supported full-arch prostheses.

PURPOSE: Long-term success of titanium dental implants is influenced by various factors, including the maintenance of good oral hygiene. The present study aimed to evaluate cleaning effectiveness and patient satisfaction with glycine powder air polishing and traditional professional oral hygiene treatments when applied to implant-supported full-arch restorations without removal of the fixed prosthesis. MATERIALS AND METHODS: A total of 85 patients with 357 implants supporting full-arch fixed restorations were included. After removal of the prosthesis (T0), the following parameters were recorded: Plaque Index, peri-implant spontaneous bleeding, probing depth and bleeding on probing. The prosthesis was then reinserted. The patients were divided into three groups, each of which received two hygiene therapies randomly administered in each hemiarch using a split-mouth design. The possible treatments were glycine powder air polishing and use of sponge floss vs sponge floss only in group 1; glycine powder air polishing vs use of an ultrasonic device with a polyetheretherketone fibre tip coating in group 2; and glycine powder air polishing vs use of carbon fibre curettes and sponge floss in group 3. After instrumentation, the prostheses were removed to assess the Plaque Index and peri-implant spontaneous bleeding. Questionnaires were used to record patients' levels of comfort and satisfaction in relation to the various treatments. RESULTS: Glycine powder air polishing resulted in a significantly higher reduction in plaque around implants compared to control treatments (sponge floss only, ultrasonic device with polyetheretherketone fibre tip coating, and manual scaling with carbon fibre curettes and use of sponge floss) (P = 0.020). Glycine powder air polishing followed by application of sponge floss provided the greatest reduction of plaque deposits on the prosthetic surfaces. On average, 80% of patients rated glycine powder air polishing highest with regard to satisfaction. CONCLUSIONS: Glycine powder air polishing is a highly effective and comfortable treatment to maintain good oral hygiene in clinical practice, and could be used as an alternative to manual and mechanical instrumentation when dealing with implant-supported restorations.

Framework Materials for Full-Arch Implant-Supported Rehabilitations: A Systematic Review of Clinical Studies.

The purpose of this systematic review was to investigate the clinical outcomes of frameworks made of different materials in patients with implant-supported full-arch prostheses. A literature search was conducted on MEDLINE, Scopus and Cochrane Library, until the 1st of March 2021, with the following search terms: framework or substructure combined with "dental implants". The outcomes evaluated were: implant and prosthesis survival, bone resorption, biological and technical complications. The Cochrane Handbook for Systematic Reviews of Interventions was employed to assess the risk of bias in randomized clinical trials. The Newcastle-Ottawa quality assessment scale was used for non-randomized studies. In total, 924 records were evaluated for title and abstract, and 11 studies were included in the review: 4 clinical randomized trials and 7 cohort studies. The framework materials investigated were: gold alloy, titanium, silver-palladium alloy, zirconia and polymers including acrylic resin and carbon-fiber-reinforced composites. High implant and prosthetic cumulative survival rates were recorded by all included studies. Various materials and different fabrication techniques are now available as alternatives to traditional cast metal frameworks, for full-arch implant-supported rehabilitations. Further long-term studies are needed to validate the use of these materials and clarify their specific clinical indications and manufacturing protocols to optimize their clinical outcomes.

MicroRNA in Implant Dentistry: From Basic Science to Clinical Application.

Specific microRNA (miRNA) expression profiles have been reported to be predictive of specific clinical outcomes of dental implants and might be used as biomarkers in implant dentistry with diagnostic and prognostic purposes. The aim of the present narrative review was to summarize current knowledge regarding the use of miRNAs in implant dentistry. The authors attempted to identify all available evidence on the topic and critically appraise it in order to lay the foundation for the development of further research oriented towards the clinical application of miRNAs in implant dentistry.

Salivary Micro-RNA and Oral Squamous Cell Carcinoma: A Systematic Review.

Oral squamous cell carcinoma (OSCC) is a widespread malignancy with high mortality. In particular, a delay in its diagnosis dramatically decreases the survival rate. The aim of this systematic review was to investigate and summarize clinical results in the literature, regarding the potential use of salivary microRNAs (miRNAs) as diagnostic and prognostic biomarkers for OSCC patients. Twelve papers were selected, including both case-control and cohort studies, and all of them detected significantly dysregulated miRNAs in OSCC patients compared to healthy controls. Based on our results, salivary miRNAs might provide a non-invasive and cost-effective method in the diagnosis of OSCC, and also to monitor more easily its evolution and therapeutic response and therefore aid in the establishment of specific therapeutic strategies.

Analysis of the Subgingival Microbiota in Implant-Supported Full-Arch Rehabilitations.

BACKGROUND: The etiology of peri-implantitis is multifactorial, and it is not directly linked to the quantitative amount of plaque. The aim of this study was to evaluate the influence of subgingival microbiota around implants supporting full-arch restorations on clinical indexes of peri-implant health. METHOD: 47 patients (54 full-arch fixed rehabilitations) were included. Based on the highest value of probing depth (PD), 47 implants (in the test arch), 40 natural teeth and 7 implants (in the antagonist arch) were selected for microbiological sampling (traditional PCR and real-time PCR). Periodontal indexes (plaque index, PlI; probing depth, PD; bleeding on probing, BOP; peri-implant suppuration, PS) and marginal bone loss were also recorded. RESULTS: Despite abundant plaque accumulation, the peri-implant parameters were within normal limits. No statistical difference was found in the microbial population around the test implants and antagonist natural teeth. Treponema denticola was present in a significantly higher amount around implants with increased PlI. Implants with increased BOP showed a significant increase in Treponema denticola and Tannerella forsythia. A significantly higher presence of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia was identified around the implants affected by peri-implantitis and in smokers. CONCLUSIONS: Peri-implantitis is characterized by a complex and polymicrobial disease, that might be influenced by the qualitative profile of plaque. Smoking might also favor implant biological complications in full-arch fixed prosthesis.

Influence of Implant Thread Morphology on Primary Stability: A Prospective Clinical Study.

OBJECTIVES: The purpose of this study was to evaluate the primary stability of two implants with the same macro- and micromorphology but different thread design and analyze their clinical outcomes over a one-year period. MATERIALS AND METHODS: 14 patients needing a partial rehabilitation with a delayed loading approach (DEL group: 9 patients) or a full-arch rehabilitation treated with immediately loaded fixed prostheses supported by 4 implants following the Columbus Bridge Protocol (CBP) (IL group: 5 patients) were included. In each patient, at least one SY (implant with standard threads) and one SL implant (implant with an augmented depth of the threads) were randomly inserted. Primary outcome measures were the number of threads exposed at a torque of 30 Ncm and 50 Ncm and final insertion torque. Secondary outcome measures were implant and prosthetic failure, peri-implant bone resorption, and periodontal parameters: bleeding on probing (BoP), plaque index (PI), and probing depth (PD) evaluated at 3, 6, and 12 months of healing. RESULTS: Nineteen SY and 19 SL implants were inserted in 14 patients. Twenty implants (10 SL and 10 SY) were inserted in the IL group, while 18 (9 SL and 9 SY) were inserted in the DEL group and followed-up for 12 months. No patients dropped out. No implants and prostheses failed. No biological complications were identified. No significant differences were found between SY and SL implants comparing the number of exposed threads when inserting the implant with a torque insertion of 30 N (T student test p = .142 and U test p = .164). At 50 N, no threads were visible in either groups. Final torque insertion values were higher for SL (mean: 48.42 Ncm) compared to SY implants (mean: 43.42 Ncm) without a statistically significant difference. All the implants showed good clinical outcomes at the 1-year-in-function visit. CONCLUSIONS: After 12 months of function, both implant types provided good clinical outcomes without statistically significant differences between the two groups. A difference in insertion torque (even if not statistically significant) was found with higher insertion torque values for SL implants with a larger thread depth.

Resveratrol treatment reduces cardiac progenitor cell dysfunction and prevents morpho-functional ventricular remodeling in type-1 diabetic rats.

Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n = 128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n = 54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n = 64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic "milieu" on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention.

Galectin-3 ablation protects mice from diet-induced NASH: a major scavenging role for galectin-3 in liver.

BACKGROUND & AIMS: Excess fatty acid oxidation and generation of reactive carbonyls with formation of advanced lipoxidation endproducts (ALEs) is involved in nonalcoholic steatohepatitis (NASH) by triggering inflammation, hepatocyte injury, and fibrosis. This study aimed at verifying the hypothesis that ablation of the ALE-receptor galectin-3 prevents experimental NASH by reducing receptor-mediated ALE clearance and downstream events. METHODS: Galectin-3-deficient (Lgals3(-/-)) and wild type (Lgals3(+/+)) mice received an atherogenic diet or standard chow for 8 months. Liver tissue was analyzed for morphology, inflammation, cell and matrix turnover, lipid metabolism, ALEs, and ALE-receptors. RESULTS: Steatosis was significantly less pronounced in Lgals3(-/-) than Lgals3(+/+) animals on atherogenic diet. NASH, invariably detected in Lgals3(+/+) mice, was observed, to a lower extent, only in 3/8 Lgals3(-/-) mice, showing less inflammatory, degenerative, and fibrotic phenomena than Lgals3(+/+) mice. This was associated with higher circulating ALE levels and lower tissue ALE accumulation and expression of other ALE-receptors. Up-regulation of hepatic fatty acid synthesis and oxidation, inflammatory cell infiltration, pro-inflammatory cytokines, endoplasmic reticulum stress, hepatocyte apoptosis, myofibroblast transdifferentiation, and impaired Akt phosphorylation were also significantly attenuated in Lgals3(-/-) animals. Galectin-3 silencing in liver endothelial cells resulted in reduced N(ε)-carboxymethyllysine-modified albumin uptake and ALE-receptor expression. CONCLUSIONS: Galectin-3 ablation protects from diet-induced NASH by decreasing hepatic ALE accumulation, with attenuation of inflammation, hepatocyte injury, and fibrosis. It also reduced up-regulation of lipid synthesis and oxidation causing less fat deposition, oxidative stress, and possibly insulin resistance. These data suggest that galectin-3 is a major receptor involved in ALE uptake by the liver.

Inhibition of notch1-dependent cardiomyogenesis leads to a dilated myopathy in the neonatal heart.

RATIONALE: Physiological hypertrophy in the developing heart has been considered the product of an increase in volume of preexisting fetal cardiomyocytes in the absence of myocyte formation. OBJECTIVE: In this study, we tested whether the mouse heart at birth has a pool of cardiac stem cells (CSCs) that differentiate into myocytes contributing to the postnatal expansion of the parenchymal cell compartment. METHODS AND RESULTS: We have found that the newborn heart contains a population of c-kit-positive CSCs that are lineage negative, self-renewing, and multipotent. CSCs express the Notch1 receptor and show the nuclear localization of its active fragment, N1ICD. In 60% of cases, N1ICD was coupled with the presence of Nkx2.5, indicating that the commitment of CSCs to the myocyte lineage is regulated by Notch1. Importantly, overexpression of N1ICD in neonatal CSCs significantly expanded the proportion of transit-amplifying myocytes. To establish whether these in vitro findings had a functional counterpart in vivo, the Notch pathway was blocked in newborn mice by administration of a gamma-secretase inhibitor. This intervention resulted in the development of a dilated myopathy and high mortality rates. Ventricular decompensation was characterized by a 62% reduction in amplifying myocytes, which resulted in a 54% decrease in myocyte number. After cessation of Notch blockade and recovery of myocyte regeneration, cardiac anatomy and function were largely restored. CONCLUSIONS: Notch1 signaling is a critical determinant of CSC growth and differentiation; when this cascade of events is altered, cardiomyogenesis is impaired, physiological cardiac hypertrophy is prevented, and a life-threatening myopathy supervenes.

The histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces cardiac arrhythmias in dystrophic mice.

AIMS: The effect of histone deacetylase inhibitors on dystrophic heart function is not established. To investigate this aspect, dystrophic mdx mice and wild-type (WT) animals were treated 90 days either with suberoylanilide hydroxamic acid (SAHA, 5 mg/kg/day) or with an equivalent amount of vehicle. METHODS AND RESULTS: The following parameters were evaluated: (i) number of ventricular arrhythmias in resting and stress conditions (restraint test) or after aconitine administration; (ii) cardiac excitability, conduction velocity, and refractoriness; (iii) expression and distribution of connexins (Cxs) and Na(v)1.5 sodium channel. Ventricular arrhythmias were negligible in all resting animals. During restraint, however, an increase in the number of arrhythmias was detected in vehicle-treated mdx mice (mdx-V) when compared with SAHA-treated mdx (mdx-SAHA) mice or normal control (WT-V). Interestingly, aconitine, a sodium channel pharmacologic opener, induced ventricular arrhythmias in 83% of WT-V mice, 11% of mdx-V, and in 57% of mdx-SAHA. Epicardial multiple lead recording revealed a prolongation of the QRS complex in mdx-V mice in comparison to WT-V and WT-SAHA mice, paralleled by a significant reduction in impulse propagation velocity. These alterations were efficiently counteracted by SAHA. Molecular analyses revealed that in mdx mice, SAHA determined Cx remodelling of Cx40, Cx37 and Cx32, whereas expression levels of Cx43 and Cx45 were unaltered. Remarkably, Cx43 lateralization observed in mdx control animals was reversed by SAHA treatment which also re-induced Na(v)1.5 expression. CONCLUSION: SAHA attenuates arrhythmias in mdx mice by a mechanism in which Cx remodelling and sodium channel re-expression could play an important role.

Modulation of actin isoform expression before the transition from experimental compensated pressure-overload cardiac hypertrophy to decompensation.

In a rat model of long-lasting pressure-overload hypertrophy, we investigated whether changes in the relative expression of myocardial actin isoforms are among the early signs of ventricular mechanical dysfunction before the transition toward decompensation. Forty-four rats with infrarenal aortic banding (AC rats) were studied. Hemodynamic parameters were measured 1 mo (AC(1) group; n = 20) or 2 mo (AC(2); n = 24) after aortic ligature. Then subgroups of AC(1) and AC(2) left ventricles (LV) were used to evaluate 1) LV anatomy and fibrosis (morphometry), 2) expression levels (immunoblotting) and spatial distribution (immunohistochemistry) of alpha-skeletal actin (alpha-SKA), alpha-cardiac actin (alpha-CA), and alpha-smooth muscle actin (alpha-SMA), and 3) cell mechanics and calcium transients in enzimatically isolated myocytes. Although the two AC groups exhibited a comparable degree of hypertrophy (+30% in LV mass; +20% in myocyte surface) and a similar increase in the amount of fibrosis compared with control animals (C group; n = 22), a worsening of LV mechanical performance was observed only in AC(2) rats at both organ and cellular levels. Conversely, AC(1) rats exhibited enhanced LV contractility and preserved cellular contractile behavior associated with increased calcium transients. Alpha-SKA expression was upregulated (+60%) in AC(1). In AC(2) ventricles, prolonged hypertension also induced a significant increase in alpha-SMA expression, mainly at the level of arterial vessels. No significant differences among groups were observed in alpha-CA expression. Our findings suggest that alpha-SKA expression regulation and wall remodeling of coronary arterioles participate in the development of impaired kinetics of contraction and relaxation in prolonged hypertension before the occurrence of marked histopathologic changes.

Notch1 regulates the fate of cardiac progenitor cells.

The Notch receptor mediates cell fate decision in multiple organs. In the current work we tested the hypothesis that Nkx2.5 is a target gene of Notch1 and raised the possibility that Notch1 regulates myocyte commitment in the adult heart. Cardiac progenitor cells (CPCs) in the niches express Notch1 receptor, and the supporting cells exhibit the Notch ligand Jagged1. The nuclear translocation of Notch1 intracellular domain (N1ICD) up-regulates Nkx2.5 in CPCs and promotes the formation of cycling myocytes in vitro. N1ICD and RBP-Jk form a protein complex, which in turn binds to the Nkx2.5 promoter initiating transcription and myocyte differentiation. In contrast, transcription factors of vascular cells are down-regulated by Jagged1 activation of the Notch1 pathway. Importantly, inhibition of Notch1 in infarcted mice impairs the commitment of resident CPCs to the myocyte lineage opposing cardiomyogenesis. These observations indicate that Notch1 favors the early specification of CPCs to the myocyte phenotype but maintains the newly formed cells in a highly proliferative state. Dividing Nkx2.5-positive myocytes correspond to transit amplifying cells, which condition the replicative capacity of the heart. In conclusion, Notch1 may have critical implications in the control of heart homeostasis and its adaptation to pathologic states.

Pim-1 regulates cardiomyocyte survival downstream of Akt.

The serine-threonine kinases Pim-1 and Akt regulate cellular proliferation and survival. Although Akt is known to be a crucial signaling protein in the myocardium, the role of Pim-1 has been overlooked. Pim-1 expression in the myocardium of mice decreased during postnatal development, re-emerged after acute pathological injury in mice and was increased in failing hearts of both mice and humans. Cardioprotective stimuli associated with Akt activation induced Pim-1 expression, but compensatory increases in Akt abundance and phosphorylation after pathological injury by infarction or pressure overload did not protect the myocardium in Pim-1-deficient mice. Transgenic expression of Pim-1 in the myocardium protected mice from infarction injury, and Pim-1 expression inhibited cardiomyocyte apoptosis with concomitant increases in Bcl-2 and Bcl-X(L) protein levels, as well as in Bad phosphorylation levels. Relative to nontransgenic controls, calcium dynamics were significantly enhanced in Pim-1-overexpressing transgenic hearts, associated with increased expression of SERCA2a, and were depressed in Pim-1-deficient hearts. Collectively, these data suggest that Pim-1 is a crucial facet of cardioprotection downstream of Akt.

Preservation of ventricular performance at early stages of diabetic cardiomyopathy involves changes in myocyte size, number and intercellular coupling.

In a rat model of diabetic cardiomyopathy, we tested whether specific changes in myocyte turnover and intercellular coupling contribute to preserving ventricular performance after a short period of hyperglycemia. In 41 rats with streptozotocin-induced diabetes and 24 control animals, cardiac electromechanical properties were assessed by telemetry ECG, epicardial potential mapping, and hemodynamic measurements to document normal ventricular function. Myocardial remodeling, expression of gap-junction proteins and myocyte regeneration were evaluated by tissue morphometry, immunohistochemistry and immunoblotting. Ventricular myocyte number and volume were also determined. In diabetic hearts, after 3 weeks of hyperglycemia, left ventricular mass was lowered by 23%, while left ventricular wall thickness and chamber volume were maintained, in the absence of fibrosis and myocyte hypertrophy. In the presence of a marked DNA oxidative damage, an increased rate of DNA replication and mitotic divisions associated with generation of new myocytes were detected. The number of cells expressing the receptor for Stem Cell Factor (c-kit) and their rate of proliferation were preserved in the left ventricle while the atrial storage of these primitive cells was severely reduced by diabetes-induced oxidative stress. Despite a down-regulation of Connexin43 and over-expression of both Connexin40 and Connexin45, the junctional proteins were normally distributed in diabetic ventricular myocardium,justifying the preserved tissue excitability and conduction velocity. In conclusion, before the appearance of the diabetic cardiomyopathic phenotype,myocardial cell proliferation associated with gap junction protein remodeling may contribute to prevent marked alterations of cardiac structure and electrophysiological properties, preserving ventricular performance.