Drp1 regulates transcription of ribosomal protein genes in embryonic hearts.

Mitochondrial dysfunction causes severe congenital cardiac abnormalities and prenatal/neonatal lethality. The lack of sufficient knowledge regarding how mitochondrial abnormalities affect cardiogenesis poses a major barrier for the development of clinical applications that target mitochondrial deficiency-induced inborn cardiomyopathies. Mitochondrial morphology, which is regulated by fission and fusion, plays a key role in determining mitochondrial activity. Dnm1l encodes a dynamin-related GTPase, Drp1, which is required for mitochondrial fission. To investigate the role of Drp1 in cardiogenesis during the embryonic metabolic shift period, we specifically inactivated Dnm1l in second heart field-derived structures. Mutant cardiomyocytes in the right ventricle (RV) displayed severe defects in mitochondrial morphology, ultrastructure and activity. These defects caused increased cell death, decreased cell survival, disorganized cardiomyocytes and embryonic lethality. By characterizing this model, we reveal an AMPK-SIRT7-GABPB axis that relays the reduced cellular energy level to decrease transcription of ribosomal protein genes in cardiomyocytes. We therefore provide the first genetic evidence in mouse that Drp1 is essential for RV development. Our research provides further mechanistic insight into how mitochondrial dysfunction causes pathological molecular and cellular alterations during cardiogenesis.

SEMA6D regulates perinatal cardiomyocyte proliferation and maturation in mice.

Cardiomyocytes undergo dramatic changes during the fetal to neonatal transition stage to adapt to the new environment. The molecular and genetic mechanisms regulating these changes remain elusive. In this study, we showed Sema6D as a novel signaling molecule regulating perinatal cardiomyocyte proliferation and maturation. SEMA6D is a member of the Semaphorin family of signaling molecules. To reveal its function during cardiogenesis, we specifically inactivated Sema6D in embryonic cardiomyocytes using a conditional gene deletion approach. All mutant animals showed hypoplastic myocardial walls in neonatal hearts due to reduced cell proliferation. We further revealed that expression of MYCN and its downstream cell cycle regulators is impaired in late fetal hearts in which Sema6D is deleted, suggesting that SEMA6D acts through MYCN to regulate cardiomyocyte proliferation. In early postnatal mutant hearts, expression of adult forms of sarcomeric proteins is increased, while expression of embryonic forms is decreased. These data collectively suggest that SEMA6D is required to maintain late fetal/early neonatal cardiomyocytes at a proliferative and less mature status. Deletion of Sema6D in cardiomyocytes led to reduced proliferation and accelerated maturation. We further examined the consequence of these defects through echocardiographic analysis. Embryonic heart deletion of Sema6D significantly impaired the cardiac contraction of male adult hearts, while having a minor effect on female mutant hearts, suggesting that the effect of Sema6D-deletion in adult hearts is sex dependent.

The effectiveness of air-free warming systems on perioperative hypothermia in total hip and knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Perioperative hypothermia is a common and serious complication during surgery. Different warming systems are used to prevent perioperative hypothermia. However, there have been no previous meta-analyses of the effectiveness of air-free warming systems on perioperative hypothermia in patients undergoing joint arthroplasty. METHODS: We systematically searched PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases to collect randomized controlled trials (RCTs) from inception to August 2018. These RCTs compared the effects of air-free warming with forced-air (FA) warming system in patients undergoing joint arthroplasty. Postoperative temperature, core temperature during surgery, thermal comfort, blood loss and incidence of shivering and hypothermia were analyzed. RESULTS: A total of 287 patients from 6 clinical studies were included in the analysis. In summary, there was no significant difference in the postoperative temperature (WMD -0.043, 95% CI -0.32 to 0.23, P = .758) between the air-free warming and FA warming groups. No statistical difference (WMD 0.058, 95% CI -0.10 to 0.22, P = .475) was found in core temperatures at 0 minutes during surgery between the air-free warming and FA warming groups. Furthermore, there was no statistical difference in thermal comfort, blood loss or incidence of shivering and hypothermia between the air-free warming and FA warming groups. CONCLUSIONS: Air-free warming system was as effective as FA warming system in patients undergoing joint arthroplasty.