Evaluation of a Wearable in-Ear Sensor for Temperature and Heart Rate Monitoring: A Pilot Study.

In the context of the COVID-19 pandemic, wearable sensors are important for early detection of critical illness especially in COVID-19 outpatients. We sought to determine in this pilot study whether a wearable in-ear sensor for continuous body temperature and heart rate monitoring (Cosinuss company, Munich) is sufficiently accurate for body temperature and heart rate monitoring. Comparing with several anesthesiologic standard of care monitoring devices (urinary bladder and zero-heat flux thermometer and ECG), we evaluated the in-ear sensor during non-cardiac surgery (German Clinical Trials Register Reg.-No: DRKS00012848). Limits of Agreement (LoA) based on Bland-Altman analysis were used to study the agreement between the in-ear sensor and the reference methods. The estimated LoA of the Cosinuss One and bladder temperature monitoring were [-0.79, 0.49] °C (95% confidence intervals [-1.03, -0.65] (lower LoA) and [0.35, 0.73] (upper LoA)), and [-0.78, 0.34] °C (95% confidence intervals [-1.18, -0.59] (lower LoA) and [0.16, 0.74] (upper LoA)) of the Cosinuss One and zero-heat flux temperature monitoring. 89% and 79% of Cosinuss One temperature monitoring were within ± 0.5 °C limit of bladder and zero-heat flux monitoring, respectively. The estimated LoA of Cosinuss One and ECG heart rate monitoring were [-4.81, 4.27] BPM (95% confidence intervals [-5.09, -4.56] (lower LoA) and [4.01, 4.54] (upper LoA)). The proportion of detection differences within ± 2BPM was 84%. Body temperature and heart rate were reliably measured by the wearable in-ear sensor.

Sexual Dysfunction Before and after Treatment of Infrarenal Aortic Aneurysm Patients.

OBJECTIVE: Sexual dysfunction is supposed to be one major complication after treatment of infrarenal aortic aneurysms. It is still controversial how many patients suffer from a sexual dysfunction already before their operation and if there are any procedure-specific differences in postoperative sexual function depending on the operative procedure performed, for example, open (OAR) or endovascular aortic repair (EVAR). METHODS: To answer these questions we conducted this prospective unicentric study using the International Index of Erectile Function (IIEF) and analyzed the sexual function of 56 male patients with an infrarenal aortic aneurysm before as well as 3, 6, and 12 months after their operation. 23 patients (median age 66.5 years) were treated by OAR and 33 patients (median age 75.8 years) by EVAR. RESULTS: We observed that the majority of the 56 patients analyzed (91.3% of the 23 OAR patients and 96.8% of the 33 EVAR patients) suffered from a sexual dysfunction already before their operation. A 56.5% of the OAR patients and 67.7% of the EVAR patients even disclaimed a severe sexual dysfunction prior to surgery. Age and operation method showed no significant influence on the IIEF score (P= 0.647 and P= 0.621, respectively). The change of the IIEF score over the 4 time points also did not significantly differ for age and operation method (P= 0.713 and P= 0.624, respectively). The IIEF scores were significantly different between time points T1 and T4 (P= 0.042), whereas between the other time points no significant differences were found. CONCLUSIONS: Sexual dysfunction is very common in infrarenal aortic aneurysm patients even before their operation. OAR and EVAR do not cause a procedure-specific deterioration of the sexual function.

The interrelationship between diabetes mellitus and peripheral arterial disease.

This systematic review examined the interrelationship between concomitant diabetes mellitus (DM) and peripheral arterial disease (PAD). The objective was to determine differences in the prevalence as well as in the outcomes in diabetic vs. non-diabetic PAD patients. The current review followed a study protocol that was published online in German in 2017. The search included societal practice guidelines, consensus statements, systematic reviews, meta-analyses, and observational studies published from 2007 to 2020 reporting symptomatic PAD and concomitant DM in patients undergoing invasive open-surgical and endovascular revascularizations. German and English literature has been considered. Eligibility criteria were verified by three independent reviewers. Disagreement was resolved by discussion involving a fourth reviewer. 580 articles were identified. After exclusion of non-eligible studies, 61 papers from 30 countries remained, respectively 850,072 patients. The included studies showed that PAD prevalence differed between diabetic vs. non-diabetic populations (20-50% vs. 10-26%), and further by age, gender, ethnicity, duration of existing diabetes, and geographic region. The included studies revealed worse outcomes regarding perioperative complications, amputation rate, and mortality rate in diabetic patients when compared to non-diabetic patients. In both groups, the amputation rates decreased during the research period. This review emphasizes an interrelationship between PAD and DM. To improve the outcomes, early detection of PAD in diabetic patients, and vice versa, should be recommended. The results of this systematic review may help to update societal practice guidelines.

Long-term incidence of cancer after index treatment for symptomatic peripheral arterial disease - a health insurance claims data analysis.

Background: Cancer as a concomitant condition in symptomatic peripheral arterial disease (PAD) patients could have an impact on further therapy and the long-term prognosis of these patients. Aim of this study was to investigate whether there is an increased incidence of cancer in PAD patients and to quantify the corresponding effect size. Materials and methods: Between January 1st, 2008 and December 31st, 2017, we analysed health insurance claims data from Germany's second-largest insurance fund, BARMER. Symptomatic PAD patients suffering from intermittent claudication (IC) or chronic limb-threatening ischaemia (CLTI) were stratified by gender at index treatment. PAD patients were then followed until an incident cancer diagnosis was recorded. To adjust for age and gender, standardized incidence ratios (SIR) were computed using the 2012 German standard population as reference. Results: 96,528 PAD patients (47% female, 44% IC, mean age 72 years) were included in the current study. When compared to the overall population, female and male PAD patients have a significantly increased risk of incident cancer of the lung (SIR 3.5 vs. 2.6), bladder (SIR 3.2 vs. 4.0), pancreas (SIR 1.4 vs. 1.6), and colon (SIR 1.3 vs. 1.3). During ten years of follow-up, some 7% of males and 4% of females developed lung cancer. For bladder, colon and pancreas cancer, the cumulative hazards were 1% vs. 3.2%, 2.2% vs. 2.8%, and 0.7% vs. 0.9%, respectively. Conclusions: Patients suffering from symptomatic PAD face a markedly higher risk for incident cancer in the long-term follow-up. The cancer risk increased continuously for certain types and PAD was strongly associated with cancer of the lung, bladder, pancreas, and colon. Taking these results into account, PAD patients could benefit from secondary and tertiary screening. These results also emphasize the impact of common risk factors such as tobacco smoke as target for health prevention.

The Association of Periodontitis and Peripheral Arterial Occlusive Disease-A Systematic Review.

Background: Observational studies support an association between periodontitis (PD) and atherosclerotic vascular disease, but little is known specifically about peripheral arterial occlusive disease (PAOD). OBJECTIVES: To systematically review the evidence for an association between PD and PAOD. DATA SOURCES: Medline via PubMed. REVIEW METHODS: We searched the Pubmed database for original studies, case reports, case series, meta-analyses and systematic reviews that assessed whether there is an association between PD (all degrees of severity) and PAOD (all degrees of severity). The reporting of this systematic review was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement following the Population, Intervention, Control, and Outcome (PICO) format. RESULTS: 17 out of 755 detected studies were included in the qualitative synthesis. Nine studies demonstrated associations between PD and PAOD, and two studies reported associations between tooth loss and PAOD. Six studies addressed the pathomechanism regarding PD as a possible trigger for PAOD. No study that dismissed an association could be detected. Odds ratios or hazard ratios ranged from 1.3 to 3.9 in four large cohort studies after adjusting for established cardiovascular risk factors. CONCLUSIONS: The presented evidence supports a link between PD and PAOD. Further studies which address the temporality of PD and PAOD and randomized controlled intervention trials examining the causal impact of PD on PAOD are needed. Although our results cannot confirm a causal role of PD in the development of PAOD, it is likely that PD is associated with PAOD and plays a contributing role.

Elafin Treatment Rescues EGFR-Klf4 Signaling and Lung Cell Survival in Ventilated Newborn Mice.

Mechanical ventilation with O2-rich gas (MV-O2) inhibits alveologenesis and lung growth. We previously showed that MV-O2 increased elastase activity and apoptosis in lungs of newborn mice, whereas elastase inhibition by elafin suppressed apoptosis and enabled lung growth. Pilot studies suggested that MV-O2 reduces lung expression of prosurvival factors phosphorylated epidermal growth factor receptor (pEGFR) and Krüppel-like factor 4 (Klf4). Here, we sought to determine whether apoptosis and lung growth arrest evoked by MV-O2 reflect disrupted pEGFR-Klf4 signaling, which elafin treatment preserves, and to assess potential biomarkers of bronchopulmonary dysplasia (BPD). Five-day-old mice underwent MV with air or 40% O2 for 8-24 hours with or without elafin treatment. Unventilated pups served as controls. Immunoblots were used to assess lung pEGFR and Klf4 proteins. Cultured MLE-12 cells were exposed to AG1478 (EGFR inhibitor), Klf4 siRNA, or vehicle to assess effects on proliferation, apoptosis, and EGFR regulation of Klf4. Plasma elastase and elafin levels were measured in extremely premature infants. In newborn mice, MV with air or 40% O2 inhibited EGFR phosphorylation and suppressed Klf4 protein content in lungs (vs. unventilated controls), yielding increased apoptosis. Elafin treatment inhibited elastase, preserved lung pEGFR and Klf4, and attenuated the apoptosis observed in lungs of vehicle-treated mice. In MLE-12 studies, pharmacological inhibition of EGFR and siRNA suppression of Klf4 increased apoptosis and reduced proliferation, and EGFR inhibition decreased Klf4. Plasma elastase levels were more than twofold higher, without a compensating increase of plasma elafin, in infants with BPD, compared to infants without BPD. These findings indicate that pEGFR-Klf4 is a novel prosurvival signaling pathway in lung epithelium that MV disrupts. Elafin preserves pEGFR-Klf4 signaling and inhibits apoptosis, thereby enabling lung growth during MV. Together, our animal and human data raise the question: would elastase inhibition prevent BPD in high-risk infants exposed to MV-O2?

Elafin Reverses Pulmonary Hypertension via Caveolin-1-Dependent Bone Morphogenetic Protein Signaling.

RATIONALE: Pulmonary arterial hypertension is characterized by endothelial dysfunction, impaired bone morphogenetic protein receptor 2 (BMPR2) signaling, and increased elastase activity. Synthetic elastase inhibitors reverse experimental pulmonary hypertension but cause hepatotoxicity in clinical studies. The endogenous elastase inhibitor elafin attenuates hypoxic pulmonary hypertension in mice, but its potential to improve endothelial function and BMPR2 signaling, and to reverse severe experimental pulmonary hypertension or vascular pathology in the human disease was unknown. OBJECTIVES: To assess elafin-mediated regression of pulmonary vascular pathology in rats and in lung explants from patients with pulmonary hypertension. To determine if elafin amplifies BMPR2 signaling in pulmonary artery endothelial cells and to elucidate the underlying mechanism. METHODS: Rats with pulmonary hypertension induced by vascular endothelial growth factor receptor blockade and hypoxia (Sugen/hypoxia) as well as lung organ cultures from patients with pulmonary hypertension were used to assess elafin-mediated reversibility of pulmonary vascular disease. Pulmonary arterial endothelial cells from patients and control subjects were used to determine the efficacy and mechanism of elafin-mediated BMPR2 signaling. MEASUREMENTS AND MAIN RESULTS: In Sugen/hypoxia rats, elafin reduced elastase activity and reversed pulmonary hypertension, judged by regression of right ventricular systolic pressure and hypertrophy and pulmonary artery occlusive changes. Elafin improved endothelial function by increasing apelin, a BMPR2 target. Elafin induced apoptosis in human pulmonary arterial smooth muscle cells and decreased neointimal lesions in lung organ culture. In normal and patient pulmonary artery endothelial cells, elafin promoted angiogenesis by increasing pSMAD-dependent and -independent BMPR2 signaling. This was linked mechanistically to augmented interaction of BMPR2 with caveolin-1 via elafin-mediated stabilization of endothelial surface caveolin-1. CONCLUSIONS: Elafin reverses obliterative changes in pulmonary arteries via elastase inhibition and caveolin-1-dependent amplification of BMPR2 signaling.

RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension.

RATIONALE: Pulmonary arterial hypertension is characterized by endothelial dysregulation, but global changes in gene expression have not been related to perturbations in function. OBJECTIVES: RNA sequencing was used to discriminate changes in transcriptomes of endothelial cells cultured from lungs of patients with idiopathic pulmonary arterial hypertension versus control subjects and to assess the functional significance of major differentially expressed transcripts. METHODS: The endothelial transcriptomes from the lungs of seven control subjects and six patients with idiopathic pulmonary arterial hypertension were analyzed. Differentially expressed genes were related to bone morphogenetic protein type 2 receptor (BMPR2) signaling. Those down-regulated were assessed for function in cultured cells and in a transgenic mouse. MEASUREMENTS AND MAIN RESULTS: Fold differences in 10 genes were significant (P < 0.05), four increased and six decreased in patients versus control subjects. No patient was mutant for BMPR2. However, knockdown of BMPR2 by siRNA in control pulmonary arterial endothelial cells recapitulated 6 of 10 patient-related gene changes, including decreased collagen IV (COL4A1, COL4A2) and ephrinA1 (EFNA1). Reduction of BMPR2-regulated transcripts was related to decreased ß-catenin. Reducing COL4A1, COL4A2, and EFNA1 by siRNA inhibited pulmonary endothelial adhesion, migration, and tube formation. In mice null for the EFNA1 receptor, EphA2, versus control animals, vascular endothelial growth factor receptor blockade and hypoxia caused more severe pulmonary hypertension, judged by elevated right ventricular systolic pressure, right ventricular hypertrophy, and loss of small arteries. CONCLUSIONS: The novel relationship between BMPR2 dysfunction and reduced expression of endothelial COL4 and EFNA1 may underlie vulnerability to injury in pulmonary arterial hypertension.

Clinical outcome of short-term compression after sclerotherapy for telangiectatic varicose veins.

BACKGROUND: Sclerotherapy is considered to be the method of choice for the treatment of telangiectatic varicose veins (C1 veins). Whereas the use of compression stockings after sclerotherapy is recommended, little is known about the impact of compression on the outcome of sclerotherapy. The aim of this study was to assess the influence of compression on the outcome of injection sclerotherapy of C1 varicose veins. METHODS: There were 100 legs of 50 consecutive patients with chronic venous insufficiency (C1) included. After randomization per patient, both legs were treated with sclerotherapy in a predefined area of the thigh (measuring 100 cm2), followed by eccentric compression for 24 hours. Group A received no further compression, whereas group B was additionally equipped with compression stockings of 18 to 20 mm Hg above the ankle and continued wearing these for 1 week. Photodocumentation was performed before, 1 week after, and 4 weeks after sclerotherapy, and the clinical outcome was assessed at these postprocedure follow-up dates. The photographs were reviewed by an internal unblinded rater and an independent blinded external rater. RESULTS: There was no discernible difference between the groups in terms of clinical outcome or side effects after 4 weeks. Whereas inter-rater reliability was high, there was no correlation between the raters and patients in terms of outcome. In 55% of the treated legs, the patients deemed the result of the treatment to be good; in 27% of the treated legs, fair; and in 18%, poor. Postprocedure hyperpigmentation occurred in 13% of patients and was comparable in both groups. Compression therapy was found to be comfortable by the majority (58%) of patients. CONCLUSIONS: One week of postinterventional compression therapy had no clinical benefit compared with no compression.

Accuracy evaluation of patient-specific 3D-printed aortic anatomy.

INTRODUCTION: 3D printing has a wide range of applications in medicine. In surgery, this technique can be used for preoperative planning of complex procedures, production of patient specific implants, as well as training. However, accuracy evaluations of 3D vascular models are rare. OBJECTIVES: Aim of this study was to investigate the accuracy of patient-specific 3D-printed aortic anatomies. METHODS: Patients suffering from aorto-iliac aneurysms and with indication for treatment were selected on the basis of different anatomy and localization of the aneurysm in the period from January 1st 2014 to May 27th 2016. Six patients with aorto-iliac aneurysms were selected out of the database for 3D-printing. Subsequently, computed tomography (CT) images of the printed 3D-models were compared with the original CT data sets. RESULTS: The mean deviation of the six 3D-vascular models ranged between -0.73 mm and 0.14 mm compared to the original CT-data. The relative deviation of the measured values showed no significant difference between the 3D-vascular and the original patient CT-data. CONCLUSION: Our results showed that 3D printing has the potential to produce patient-specific 3D vascular models with reliable accuracy. This enables the use of such models for the development of new endovascular procedures and devices.

Vivostat Platelet-Rich Fibrin® for Complicated or Chronic Wounds-A Pilot Study.

Vivostat Platelet-Rich Fibrin® (PRF) is an autologous platelet concentrate used for the local treatment of chronic or complicated wounds. Still, its application for this indication is not evidence-based. Therefore, we performed this monocentric retrospective pilot study investigating the clinical outcome of a local treatment of chronic or complicated wounds in 35 patients (23 male, 12 female, mean age 68.7 years) treated with Vivostat PRF®. This study population is the largest among published studies analyzing the clinical efficacy of Vivostat PRF® on chronic wounds so far. Using the perpendicular method we divided the wounds into three sizes (<10, 10-30, and >30 cm2). The clinical efficacy of the Vivostat PRF treatment was the primary endpoint and was divided into three groups of increasing degrees of wound improvement: (1) no improvement of the wound (wound area was not reduced > 10% under Vivostat PRF® treatment), (2) improvement of the wound (reduced area > 10% under Vivostat PRF® treatment) and (3) complete epithelialization (wounds that were completely re-epithelialized after Vivostat PRF® treatment). We included patients' diagnosis and concomitant diseases (peripheral arterial occlusive disease (PAOD)), chronic venous insufficiency (CVI)), diabetic foot syndrome (DFS)) in our data analysis in order to investigate their potential impact on the wound healing capacity of Vivostat PRF®. Our results show that in the entire study population, 13 out of 35 (37.1%) patients experienced wound improvement and 14 out of 35 (40%) patients showed complete epithelialization of their wound under Vivostat PRF® treatment. In summary, 77.1% of the treated patients benefited from the Vivostat PRF® therapy. These positive wound healing effects were all observed within the first three to six Vivostat PRF® applications. Subgroup analyses showed that Vivostat PRF® appeared to be more efficient in patients without CVI in comparison to patients with CVI (p = 0.02). Moreover, Vivostat PRF® treatment seems to be particularly efficient in PAOD-related wounds with a reduced crural arterial blood supply (p = 0.01). Additionally, we performed an experimental human in vivo study on ten male students where we artificially generated bilateral gluteal wounds and analyzed the influence of the Vivostat PRF® treatment on the expression of two genes (human beta Defensin-2, ((hBD-2) and human beta-Defensin-3 (hBD-3)) in keratinocytes of resected wound specimens that are induced during wound healing. Interestingly, this analysis revealed that only seven of out ten individuals showed a relevant hBD-2 and hBD-3 gene induction after Vivostat PRF® treatment. This led to the novel "key-lock-hypothesis". With the goal of an individualized precision medicine approach with optimized wound treatment strategies in the future, this is an important observation that demands further experimental and clinical studies.

Feasibility of an endovascular training and research environment with exchangeable patient specific 3D printed vascular anatomy: Simulator with exchangeable patient-specific 3D-printed vascular anatomy for endovascular training and research.

PURPOSE: Endovascular interventions have become standard procedures for the therapy of abdominal aortic aneurysms. Therefore, endovascular surgeons need special skills which have to be learned and trained. Additionally, authentic simulators are needed for further development of new endovascular devices and procedures. The aim of this project was to develop an authentic and modular endovascular simulation environment with patient-specific vascular anatomy for training and research purposes. MATERIAL AND METHODS: We first designed a prototype with exchangeable 3D-printed patient-specific vascular anatomy. Then, the feasibility of the prototype was validated by a simulation of an EVAR procedure in a clinical setting. RESULTS: We developed an authentic endovascular simulator with an exchangeable patient-specific vascular anatomy and performed an EVAR procedure under realistic conditions. The evaluation of the accuracy of the vascular models showed little deviation when compared with the original CT data. CONCLUSION: Endovascular simulators based on patient-specific 3D-printed vascular models can realistically mimic endovascular procedures and have the potential to be used for further development of new devices and grafts as well as for training purposes. Furthermore, in our opinion they can reduce the use of animals during developmental processes.

PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis.

Using proteomic approaches, we uncovered a DNA damage response (DDR) function for peroxisome proliferator activated receptor γ (PPARγ) through its interaction with the DNA damage sensor MRE11-RAD50-NBS1 (MRN) and the E3 ubiquitin ligase UBR5. We show that PPARγ promotes ATM signaling and is essential for UBR5 activity targeting ATM interactor (ATMIN). PPARγ depletion increases ATMIN protein independent of transcription and suppresses DDR-induced ATM signaling. Blocking ATMIN in this context restores ATM activation and DNA repair. We illustrate the physiological relevance of PPARγ DDR functions by using pulmonary arterial hypertension (PAH) as a model that has impaired PPARγ signaling related to endothelial cell (EC) dysfunction and unresolved DNA damage. In pulmonary arterial ECs (PAECs) from PAH patients, we observed disrupted PPARγ-UBR5 interaction, heightened ATMIN expression, and DNA lesions. Blocking ATMIN in PAH PAEC restores ATM activation. Thus, impaired PPARγ DDR functions may explain the genomic instability and loss of endothelial homeostasis in PAH.

Management of acute aortic thrombosis.

Acute aortic thrombosis (AAT) is a rare life threatening event that leads to a sudden occlusion of the aorta. The mortality and morbidity of AAT is still high despite modern surgical techniques. Usually it is the result of a large saddle embolus to the aortic bifurcation, in situ thrombosis of an atherosclerotic aorta or acute occlusion of an abdominal aortic aneurysm. Clinical symptoms depend on the level of the aortic occlusion and can be mistaken for a stroke or similar neurological disease. The combination of age and advanced cardiac disease seems to be significant risks factors for AAT. In patients who have no cardiac or vascular disease this catastrophic event is very rare and is mostly due to hypercoagulable disorders. Revascularization of the ischemic organ/limb as soon as possible is the major aim in the therapy of AAT to avoid further ischemic damage. Surgical reperfusion is the first line approach. If the accepting clinic has no facilities for an immediate surgical intervention it is of primary importance that these patients should be referred to an appropriate center for further management. Paradox seems the fact that most of the patients die as a consequence of reperfusion injury/postperfusion syndrome that occurs after revascularization of acute ischemic limbs.

Biodistribution and pharmacokinetics of the (99m)Tc labeled human elastase inhibitor, elafin, in rats.

Elafin is a potent reversible inhibitor of the pro-inflammatory proteases leukocyte elastase and protease 3. It is currently in clinical development for the use in postoperative inflammatory diseases. We investigated the pharmacokinetics of (99m)Tc-labeled elafin ((99m)Tc-Elafin) in blood and individual organs in rat after bolus intravenous injection using the single photon emission tomography (SPECT). (99m)Tc-Elafin predominantly accumulated in the kidney reaching a maximum of 8.5% ± 0.1% of the injected dose per gram (ID/g) at 5 min post injection (p.i) and decreased only slowly during 24 h. In contrast, the initially high radio activity recorded in the other organs rapidly decreased parallel to the radioactivity detected in blood. The blood kinetics fits to a two compartment kinetics model. The radio activity in the dissected kidney was 4.98 ± 1.24%ID/g 24 h p.i, while in other organs, including the brain, no accumulation of (99m)Tc-Elafin was detected. At this time point 30% of the detected radioactivity in the kidney was identified to be not metabolized (99m)Tc-Elafin. In conclusion, the blood and organ-specific kinetic data provide a basis for planning of adequate dosing regimens and the high accumulation of intact elafin in the kidney favors clinical developments targeting inflammatory kidney diseases, such as chronic allograft nephropathy after kidney transplantation.

BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension.

Mitochondrial dysfunction, inflammation, and mutant bone morphogenetic protein receptor 2 (BMPR2) are associated with pulmonary arterial hypertension (PAH), an incurable disease characterized by pulmonary arterial (PA) endothelial cell (EC) apoptosis, decreased microvessels, and occlusive vascular remodeling. We hypothesized that reduced BMPR2 induces PAEC mitochondrial dysfunction, promoting a pro-inflammatory or pro-apoptotic state. Mice with EC deletion of BMPR2 develop hypoxia-induced pulmonary hypertension that, in contrast to non-transgenic littermates, does not reverse upon reoxygenation and is associated with reduced PA microvessels and lung EC p53, PGC1α and TFAM, regulators of mitochondrial biogenesis, and mitochondrial DNA. Decreasing PAEC BMPR2 by siRNA during reoxygenation represses p53, PGC1α, NRF2, TFAM, mitochondrial membrane potential, and ATP and induces mitochondrial DNA deletion and apoptosis. Reducing PAEC BMPR2 in normoxia increases p53, PGC1α, TFAM, mitochondrial membrane potential, ATP production, and glycolysis, and induces mitochondrial fission and a pro-inflammatory state. These features are recapitulated in PAECs from PAH patients with mutant BMPR2.