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The incidence of cardiac disease is age and sex dependent, but the mechanisms governing these associations remain poorly understood. Mitochondria are the organelles in charge of producing energy for the cells, and their malfunction has been linked to cardiovascular disease and heart failure. Interestingly, heart mitochondrial content and functionality are also age and sex dependent. Here we investigated the combinatory effects of age and sex in mitochondrial bioenergetics that could help to understand their role on cardiac disease. Cardiac mitochondria from 6- and 24-month-old male and female Wistar rats were isolated, and the enzymatic activities of the oxidative-phosphorylative complexes I, III, and IV and ATPase, as well as the protein levels of complex IV, β-ATPase, and mitochondrial transcription factor A (TFAM), were measured. Furthermore, heart DNA content, citrate synthase activity, mitochondrial protein content, oxygen consumption, and H2O2 generation were also determined. Results showed a reduction in heart mitochondrial mass and functionality with age that correlated with increased H2O2 generation. Moreover, sex-dependent differences were found in several of these parameters. In particular, old females exhibited a significant loss of mitochondrial function and increased relative H2O2 production compared with their male counterparts. The results demonstrate a sex dimorphism in the age-associated defects on cardiac mitochondrial function. [ABSTRACT FROM AUTHOR]

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Gender and diet have an important effect in cardiovascular disease and other aging-associated disorders, whose initiation and/or worsening seem to be delayed in females from different species and in animals subjected to caloric restriction (CR). The aim of the present study was to investigate whether cardiac muscle bioenergetic mitochondrial features could be responsible for these beneficial effects. Methods: Fifteen-month-old male and female Wistar rats were fed ad libitum or subjected to 40% CR for 3 months. Cardiac mitochondrial function (citrate synthase activity, oxygen consumption), activity of complexes I, III, IV and ATPase of the OXPHOS system, antioxidant activities (MnSOD, GPx), mitochondrial DNA and protein content, mitochondrial H2O2 production, heart oxidative damage, complex IV and ATPase content and efficiency, as well as protein levels of mitochondrial transcription factor A (TFAM) and peroxisome-proliferator-activated receptor-gamma co-activator 1 alpha (PGC1α) were measured. Results: Female and CR rats exhibited lower cardiac mitochondria content, which were more efficient and generated less H2O2 than in males and ad libitum fed animals, with their consequent lower heart oxidative damage. Conclusion: Higher mitochondrial differentiation becomes a metabolic adaptation to increase energy efficiency, as what happens in female and CR rats. This adaptation is associated with their lower mitochondrial free radical production and oxidative damage, which could help to understand the mechanism by which these animals exhibit a lower incidence of aging-related disorders, including cardiovascular disease. [Copyright &y& Elsevier]

Endogenous protective pathways mitigate the overshooting of inflammation after sterile or infectious injury. Here we report that formyl peptide receptor 2 (Fpr2/3) null mice display a major phenotype with exacerbated vascular inflammation observed postischemia reperfusion (IR) injury of the mesenteric artery, characterized by marked neutrophil adhesion and extravasation as visualized by intravital microscopy. Analysis of endogenous agonists for Fpr2/3 revealed that lipoxin A4 (LXA4) was generated by platelet/neutrophil aggregates during ischemia: this cellular response was attenuated in Fpr2/3-/- mice; hence, LXA4 levels were lower after 30 minutes' ischemia, and associated with augmented vascular inflammation in the reperfusion (45-180 minutes) phase. Exogenous delivery of LXA4 attenuated IR-mediated inflammation in Fpr2/3+/+ but not Fpr2/3-/- mice; conversely, an Fpr2/3 antagonist skewed the vascular phenotype of Fpr2/3+/+ mice to that of Fpr2/3-/- animals. Such LXA4-based circuit could be activated by aspirin (30-100 mg/kg), which triggered formation of 15-epi-LXA4 in wild-type mice, yet it was effective in Fpr2/3-/- mice. In summary, we propose that during ischemia, neutrophil Fpr2/3 controls platelet/neutrophil aggregates with the rapid generation of circulating LXA4, which in turn modulates downstream vascular inflammatory responses evident during the reperfusion phase. [ABSTRACT FROM AUTHOR]

Objective: Gender and diet have an important effect in cardiovascular disease and other aging-associated disorders, whose initiation and/or worsening seem to be delayed in females from different species and in animals subjected to caloric restriction (CR). The aim of the present study was to investigate whether cardiac muscle bioenergetic mitochondrial features could be responsible for these beneficial effects., Methods: Fifteen-month-old male and female Wistar rats were fed ad libitum or subjected to 40% CR for 3 months. Cardiac mitochondrial function (citrate synthase activity, oxygen consumption), activity of complexes I, III, IV and ATPase of the OXPHOS system, antioxidant activities (MnSOD, GPx), mitochondrial DNA and protein content, mitochondrial H2O2 production, heart oxidative damage, complex IV and ATPase content and efficiency, as well as protein levels of mitochondrial transcription factor A (TFAM) and peroxisome-proliferator-activated receptor-gamma co-activator 1 alpha (PGC1alpha) were measured., Results: Female and CR rats exhibited lower cardiac mitochondria content, which were more efficient and generated less H2O2 than in males and ad libitum fed animals, with their consequent lower heart oxidative damage., Conclusion: Higher mitochondrial differentiation becomes a metabolic adaptation to increase energy efficiency, as what happens in female and CR rats. This adaptation is associated with their lower mitochondrial free radical production and oxidative damage, which could help to understand the mechanism by which these animals exhibit a lower incidence of aging-related disorders, including cardiovascular disease.