Brown Adipose Tissue and BMP3b Decrease Injury in Cardiac Ischemia-Reperfusion.

BACKGROUND: Despite advances in treatment, myocardial infarction (MI) is a leading cause of heart failure and death worldwide, with both ischemia and reperfusion (I/R) causing cardiac injury. A previous study using a mouse model of nonreperfused MI showed activation of brown adipose tissue (BAT). Recent studies showed that molecules secreted by BAT target the heart. We investigated whether BAT attenuates cardiac injury in I/R and sought to identify potential cardioprotective proteins secreted by BAT. METHODS: Myocardial I/R surgery with or without BAT transplantation was performed in wild-type (WT) mice and in mice with impaired BAT function (uncoupling protein 1 [Ucp1]-deficient mice). To identify potential cardioprotective factors produced by BAT, RNA-seq (RNA sequencing) was performed in BAT from WT and Ucp1-/- mice. Subsequently, myocardial I/R surgery with or without BAT transplantation was performed in Bmp3b (bone morphogenetic protein 3b)-deficient mice, and WT mice subjected to myocardial I/R were treated using BMP3b. RESULTS: Dysfunction of BAT in mice was associated with larger MI size after I/R; conversely, augmenting BAT by transplantation decreased MI size. We identified Bmp3b as a protein secreted by BAT after I/R. Compared with WT mice, Bmp3b-deficient mice developed larger MIs. Increasing functional BAT by transplanting BAT from WT mice to Bmp3b-deficient mice reduced I/R injury whereas transplanting BAT from Bmp3b-deficient mice did not. Treatment of WT mice with BMP3b before reperfusion decreased MI size. The cardioprotective effect of BMP3b was mediated through SMAD1/5/8. In humans, the plasma level of BMP3b increased after MI and was positively correlated with the extent of cardiac injury. CONCLUSIONS: The results of this study suggest a cardioprotective role of BAT and BMP3b, a protein secreted by BAT, in a model of I/R injury. Interventions increasing BMP3b levels or targeting Smad 1/5 may represent novel therapeutic approaches to decrease myocardial damage in I/R injury.

Deficiency of bone morphogenetic protein-3b induces metabolic syndrome and increases adipogenesis.

Bone morphogenetic protein (BMP) receptor signaling is critical for the regulation of the endocrine system and cardiovascular structure and function. The objective of this study was to investigate whether Bmp3b, a glycoprotein synthetized and secreted by adipose tissue, is necessary to regulate glucose and lipid metabolism, adipogenesis, and cardiovascular remodeling. Over the course of 4 mo, Bmp3b-knockout (Bmp3b-/-) mice gained more weight than wild-type (WT) mice. The plasma levels of cholesterol and triglycerides were higher in Bmp3b-/- mice than in WT mice. Bmp3b-/- mice developed insulin resistance and glucose intolerance. The basal heart rate was higher in Bmp3b-/- mice than in WT mice, and echocardiography revealed eccentric remodeling in Bmp3b-/- mice. The expression of adipogenesis-related genes in white adipose tissue was higher in Bmp3b-/- mice than in WT control mice. In vitro studies showed that Bmp3b modulates the activity of the C/ebpα promoter, an effect mediated by Smad2/3. The results of this study suggest that Bmp3b is necessary for the maintenance of homeostasis in terms of age-related weight gain, glucose metabolism, and left ventricular (LV) remodeling and function. Interventions that increase the level or function of BMP3b may decrease cardiovascular risk and pathological cardiac remodeling.

Implementing Video to Home to Increase Access to Evidence-Based Psychotherapy for Rural Veterans.

This clinical demonstration project used facilitation to implement VA Video to Home (VTH) to deliver evidence-based psychotherapies to underserved rural Veterans, to increase access to mental health care. Participants were Veterans seeking mental health treatment at "Sonny" Montgomery Veterans Affairs Medical Center in Jackson, MS, and/or its six community-based outpatient clinics. Measures included patient encounter and demographic data, patient and provider interviews, reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) factors, measures of fidelity to manualized evidence-based psychotherapies (EBPs), and qualitative interviews. The project was deemed feasible; 93 (67 men, 26 women, including 77 rural, 16 urban) patients received weekly EBPs via VTH. Nearly half were Black (n = 46), 36 of whom (78.3%) were also rural. Fifty-three (48.4%) were Operation Enduring Freedom/Operation Iraqi Freedom Veterans. Ages varied widely, from 20 to 79 years. Primary diagnoses included posttraumatic stress disorder (41), depressive disorders (22), anxiety disorders (nine), insomnia (eight), chronic pain (eight), and substance use disorder (five). Fifteen clinicians were trained to deliver eight EBPs via VTH. Growth in number of Veterans treated by telehealth was 10.12 times and mental health visits were 7.34 times greater than the national annual average of growth for telehealth at VHA facilities. Illustrative examples and qualitative data from both patients and providers suggested overall satisfaction with VTH. This demonstrates the benefits of VTH for increasing access to mental health treatment for rural patients and advantages of an implementation facilitation strategy using an external facilitator. Continuing research should clarify whether certain patients are more likely to participate than others and whether certain EBPs are more easily delivered with VTH than others.

The convergent validity of the trauma symptom checklist for young children for a sample of sexually abused outpatients.

The convergent validity of the Trauma Symptom Checklist for Young Children (TSCYC) was examined with a sample of 172 sexually abused outpatient treatment-seeking children and their caregivers. The TSCYC evidenced good convergent validity with other parent ratings (e.g., the Child Behavior Checklist, Child Sexual Behavior Inventory, and the University of California at Los Angeles Post-Traumatic Stress Disorder Reaction Index [UCLA PTSD Index]). The convergent validity of the TSCYC and the Trauma Symptom Checklist for Children was weak, perhaps illustrating the lack of agreement often found between children and caregivers and illustrating the need for a multi-informant approach to screening and assessment of sexually abused children. The TSCYC seems to hold promise based on the emerging evidence for its convergent validity.