Microvascular ischemia is common, particularly in the setting of critical illness. We need better ways to evaluate, diagnose and treat these conditions, whether they relate to microvascular myocardial ischemia, as a primary diagnosis of complication of other acute illness, or non-myocardial ischemia during the course of surgery, injury, infection or acute illness.
Does interrupted or aberrant pulmonary vascular development contribute to pulmonary hypertension?
Does treatment with spironolactone improve outcomes in patients with pulmonary arterial hypertension (and/or pulmonary hypertension associated with diffuse parenchymal lung disease or COPD)? Spironolactone has been shown beneficial in CHF and many of the same mechanisms are at plan in RV failure from pulmonary hypertension. Again, no clear evidence whether this is a useful treatment or not, and no evidence to guide ...more »
Does anticoagulation with warfarin improve outcomes (time to clinical worsening, qualtiy of life, exercise capacity) in patients with pulmonary arterial hypertension treated with current oral/inhaled therapies? There are substantial "unknowns" and practice variation in anticoagulation in PAH. Resource utilization is also a factor here. We may either be helping patients (or hurting them with side effects) by using anticoagulation. ...more »
Clinical trials involving administration of antioxidants such as vitamin C or vitamin E as therapeutic strategies for cardiovascular diseases associated with oxidant stress have proven to be surprisingly disappointing. A particularly attractive alternative approach is direct upregulation of endogenous antioxidant defenses such as NRF2 via dietary approaches. NRF2 is a master antioxidant and cell protective transcription ...more »
Does "goal-targeted" therapy (with adjustments/additional therapy, if certain "goals" are not achieved) improve quality of life, functional status, and survival in patients with pulmonary arterial hypertension? Trials of therapies for hepatopulmonary syndrome.
How do gene mutations in endoglin and alk 1 create arteriovenous malformations leading to disease. Alk 1 and endoglin are receptors in TGFB/BMP family signaling. TGFB/BMP have roles in vascular development, remodeling and maintenance in vascular integrity. Understanding the downstream effect will lead to advancements in reducing genetic diseases such as HHT as well as vascular malformations in general
How can we better model human vascular disease in all its complexity?
This is key to more effective translation of both diagnostics and therapeutics. Develop improved animal models of vascular diseases including PAD, aneurysm, venous diseases, to facilitate fundamental research and preclinical development.
Does screening for asymptomatic vascular disease increase awareness, promote compliance with lifestyle interventions, and improve overall health?
Why loss of endoglin causes HHT is not known. Endoglin is expressed by vascular smooth muscle cells and endothelial cells.
What is the role of endogin on vascular smooth muscle cells and why its loss contributes to HHT and other vascular malformations
the role of pro-inflammatory mechanisms of vascular disease are well characterized, but we know little about potentially protective endogenous anti-inflammatory mechanisms.
What are the causative factors underlying the disparity in prevalence and progression of various vascular disorders (PAD, CVD, aneurysm) across populations?