Survivin May Be a Potential Biomarker of Successful PAH Surgery in CHD, Study Shows - Pulmonary Hypertension News
Survivin May Be a Potential Biomarker of Successful PAH Surgery in CHD, Study Shows - Pulmonary Hypertension News |
| Posted: 26 Aug 2019 05:00 AM PDT The levels of survivin protein in the blood may help determine if surgery to treat pulmonary arterial hypertension (PAH) will be successful in people with congenital heart disease (CHD), according to new research. Findings in a rat model of PAH also suggest that the amount of survivin may help predict the extent of lung lesions in these patients. The study, "The expression of survivin in irreversible pulmonary arterial hypertension rats and its value in evaluating the reversibility of pulmonary arterial hypertension secondary to congenital heart disease," was published in the journal Pulmonary Circulation. PAH is a common complication of CHDs that are characterized by impaired oxygenated-venous blood separation. Whether or not PAH is reversible determines the success of surgery to close the shunts, or holes in the heart that allow the blood from the heart's left and the right sides to get mixed. However, no existing methods or biomarkers are widely established to predict PAH progress in people with congenital heart defects. Previous studies have demonstrated that resistance to apoptosis — "programmed" cell death, as opposed to death caused by injury — is a key mechanism of both vascular endothelial cells (those that line the interior of blood vessels) and smooth muscle cells that contributes to the irreversibility of PAH. Apoptosis-related markers have been suggested as potential tools for improving diagnostic accuracy and providing information on the prognosis of cancer. Experiments also have demonstrated that using the chemotherapy daunorubicin could reduce pulmonary arterial wall thickness by boosting apoptosis. Supporting this hypothesis, levels of survivin — a member of inhibitor of apoptosis proteins family — are markedly increased and help determine prognosis in diverse cancer types. Yet, whether this protein may be useful in PAH remains unclear. Researchers from Capital Medical University, in Beijing, and University of Iowa Carver College of Medicine addressed this knowledge gap in a rat model of irreversible PAH induced by injecting a natural plant toxin called monocrotaline following left lung removal. Survivin's potential as a biomarker of PAH reversibility also was investigated in 60 patients with CHD. Animals with irreversible PAH showed prominent obstructive lesions due to proliferation of cells from the inner layer of small lung arteries. This was associated with reduced apoptosis and with marked increased in both the number of cells containing survivin, and the circulating blood levels of this protein. In turn, rats with reversible PAH showed a less accentuated increase in mean pulmonary arterial pressure (mPAP), and no changes in an index of right ventricular enlargement relative to the CHD animals without PAH. In addition, unlike those with irreversible disease, these animals showed no decrease in cardiac index — which takes into account cardiac output and body surface area. They also exhibited enlargement of the arterial medial layer, resulting in mild vessel blockage, with increased apoptosis, and unaltered survivin levels compared with the controls. In all rats, the higher the blood levels of survivin, the greater the amount of this protein in the lungs. Supported by these findings, the team believes that high levels of "survivin may be correlated with the extent of pulmonary [disease-associated] lesions, as in tumors." Among the patients, the classification of irreversible or reversible PAH was based on whether mPAP remained high or was normalized after surgery. Those with irreversible PAH (22 patients with a mean age of 29 years, of whom 13 were females) showed higher blood levels of survivin before surgery than those with reversible PAH (38 patients; mean age 22.5 years, 21 women), and CHD patients without PAH (control group). Survivin blood levels were found to be correlated with pre-surgery pulmonary vascular resistance and both post-surgery mPAP, and change in mPAP. Subsequent analysis showed that survivin levels above or below 27.5 pg/mL could help define the outcome of surgery in CHD patients with a sensitivity of 89.5% and a specificity of 68.2%. Both reversible and irreversible PAH patients showed increased levels of the cardiac disease biomarker brain natriuretic peptide (BNP). However, this increase was more pronounced in participants with irreversible changes. Higher blood levels of survivin correlated with greater amounts of BNP. "In conclusion, the increased survivin level is a feature of irreversible PAH and the serum survivin represents a candidate biomarker reflecting the operability of CHD-PAH patients," researchers said. Studies with longer follow-up and a larger number of patients are needed to validate these findings, the team cautioned.  José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer's disease. × José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer's disease. Latest Posts  |
| Advocate for Your Child's Education - Pulmonary Hypertension News Posted: 26 Aug 2019 07:00 AM PDT Pulmonary hypertension (PH) has a ripple effect on family life. A diagnosis is like a pebble tossed into water, its weight disrupting the calm with waves of change. My advice is to wade through those ripples and rescue some normalcy. It might take time to calm the waters, but your patience will be rewarded. One of our many concerns when my son was diagnosed was how PH was going to affect his education. As summer ends, it's a good time for me to share tips on how to advocate for PH children who are returning to school. There will be academic and social challenges, but if you are as motivated to communicate with school staff as you are with your child's medical team, a functioning new normal can be reached. If you're lucky and your student's school has a registered nurse, he or she can be an asset in addressing your child's medical needs. My son, however, attended a small, private Catholic grade school where the administrative assistant wore many hats, including that of a non-registered nurse. Understandably, she felt overwhelmed and unprepared to be held responsible for a child with extensive medical needs. My son was on complicated, continuous IV therapy, taking numerous medications with the potential for serious side effects. Any emergencies would require a quick response and special care until paramedics arrived. It was a huge responsibility to place on the shoulders of the administrative assistant, teachers, and other staff. I completely understood the worry, but I was desperate to save this part of my son's pre-PH life. For the benefit of his mental wellness, he needed to return to his friends and the comfort of a familiar setting. Luckily, I was employed as the parish secretary and worked in the building across the parking lot from the school. This meant that at a moment's notice, I could be at my son's side and relieve the administrative assistant in the event of an emergency. I could also help with any other concerns. It's convenient if you work close to your child's school, but most parents probably do not. An option for stay-at-home parents or those with a flexible work schedule would be to take advantage of volunteer opportunities at their child's school. This lets them be helpful in more ways than one. Whatever your arrangement and whether a school nurse is on staff or not, there is an additional protective measure that I recommend PH parents take. Request a staff meeting to explain and answer questions regarding PH and its symptoms, cover the complexities of PH treatments, and address their side effects. People in the PH community commonly use Accredo Specialty Pharmacy. What they might not know is that they can schedule an Accredo nurse to visit their child's school and speak to the staff on their behalf. At the start of every school year since diagnosis, this is what I have arranged. The nurse helped explain PH and answer questions. She also provided hands-on education regarding the CADD-Legacy pump and how it administers continuous IV Flolan (epoprostenol GM) through a central line leading to my son's chest. She familiarized the staff with the pump alarm and how to troubleshoot any malfunction it might experience. The staff was informed of how critical Flolan was to keeping my son stable and how serious it would be if he suddenly stopped receiving it. The nurse also covered other PH medications such as Revatio (sildenafil) and Tracleer (bosentan), and explained how vasodilators can give patients a flushed appearance, making them look healthier than they really are. She discussed side effects, especially proneness to migraines. She also highlighted my son's special needs that would require patience and understanding: frequent use of the restroom because of diuretics, inability to partake in most gym activities, and the need to remain indoors during extremely hot or cold weather. An IEP or 504 plan can also help address these and other needs and concerns. At the start of every school year, I gathered PH resources and created an extensive list of medications, emergency contacts, and other pertinent information, and organized it all into a binder. This was kept at the front office, in the administrative assistant's care. If Murphy's Law struck and I couldn't be reached during an emergency, the staff was well-prepared to help my son. Consider providing support to your child's classmates by having someone — a teacher, an Accredo nurse, or yourself — carefully explain PH to them. They, too, will have questions and will need help understanding what their friend is going through. Also, reach out to their parents by offering PH resources. I recommend the free PH wallet cards available through the Pulmonary Hypertension Association. Thanks to advocacy and enormous support, my son attended this school for five years while living with PH, and graduated from eighth grade with his friends. I wish all students, including happy home-schoolers, a successful school year that is medically uneventful. *** Note: Pulmonary Hypertension News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Pulmonary Hypertension News or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to pulmonary hypertension.  ×  |
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