Figure 6 - available via license: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
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Role of APN in the crosstalk between the heart and lung. APN, adiponectin; PAEcs, pulmonary artery endothelial cells; ROS, reactive oxygen species.
Source publication
Left heart disease is the main cause of clinical pulmonary arterial hypertension (PAH). Common types of left heart disease that result in PAH include heart failure, left ventricular systolic dysfunction, left ventricular diastolic dysfunction and valvular disease. It is currently believed that mechanical pressure caused by high pulmonary venous pre...
Context in source publication
Context 1
... a negative role in the BMP signaling pathway described earlier in this article. Thus, the research on the role of adiponectin in pulmonary vessels has been insufficient thus far. However, the abovementioned evidence provides new clues regarding the role of adiponectin in the heart and lungs and the pathological mechanism underlying post-MI PAH (Fig. ...
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Citations
... Although AMI may lead to post-capillary pulmonary hypertension by increasing left ventricular filling pressure, whether PH also contributes to AMI by compromising coronary perfusion and worsening myocardial ischemia remains unclear. 6,10,11 Recently, a review article focusing on the pathophysiological effects in individuals with AMI and PH emphasized an internal imbalance and dysregulation between the heart and lungs. 10 Beyond the main therapeutic targets of endothelin 1, nitric oxide (NO) and prostacyclin in PH, other signaling pathways including the renin-angiotensin-aldosterone system and vascular endothelial growth factor may overlap in the pathologic mechanism of both PH and AMI. ...
... 6,10,11 Recently, a review article focusing on the pathophysiological effects in individuals with AMI and PH emphasized an internal imbalance and dysregulation between the heart and lungs. 10 Beyond the main therapeutic targets of endothelin 1, nitric oxide (NO) and prostacyclin in PH, other signaling pathways including the renin-angiotensin-aldosterone system and vascular endothelial growth factor may overlap in the pathologic mechanism of both PH and AMI. 6,10,12,13 Nevertheless, given a relatively limited lifespan of patients with PH, long-term epidemiologic information regarding the incidence of AMI or ischemic stroke post the diagnosis of PH is currently lacking. ...
... 10 Beyond the main therapeutic targets of endothelin 1, nitric oxide (NO) and prostacyclin in PH, other signaling pathways including the renin-angiotensin-aldosterone system and vascular endothelial growth factor may overlap in the pathologic mechanism of both PH and AMI. 6,10,12,13 Nevertheless, given a relatively limited lifespan of patients with PH, long-term epidemiologic information regarding the incidence of AMI or ischemic stroke post the diagnosis of PH is currently lacking. A meta-analysis reported that 8% of patients with PH had ischemic stroke, 14 which is similar to our findings (6%). ...
Background:
Sildenafil, a phosphodiesterase-5 inhibitor, has been approved for the treatment of pulmonary hypertension (PH). It improves exercise capacity, symptoms and hemodynamics in patients with PH by lowering pulmonary pressures. Preclinical studies have indicated a possible protective effect of sildenafil on ischemia/reperfusion injury. Nevertheless, evidence showing the impact of sildenafil on ischemic disorders in patients with PH is lacking.
Methods:
Using the Taiwanese National Health Insurance Research Database and Cause of Death databases, we conducted a retrospective cohort study to investigate the hazard ratio (HR) with inverse probability of treatment weighting (IPTW) of sildenafil for the development of major adverse cardiovascular and cerebrovascular events (MACCEs), including new-onset acute myocardial infarction (AMI) and ischemic stroke in patients with PH. The follow-up period was 7 years. In addition, we performed sensitivity analysis by limiting the studied population to those who received right heart catheterization and excluding those with a history of coronary arterial disease.
Results:
After adjusting for age, sex and comorbidities, the patients receiving sildenafil had a significantly lower risk of subsequent AMI [adjusted HR with IPTW: 0.42; confidence interval (CI): 0.20-0.86] and a trend of less ischemic stroke (adjusted HR with IPTW: 0.72; CI: 0.51-1.02). Interestingly, among the sildenafil users, those who were older, had chronic kidney disease, and took cardiovascular medications showed the most significant reductions in the risk of MACCEs. The sensitivity analysis showed similar results.
Conclusions:
The use of sildenafil in patients with PH was associated with a lower risk of long-term MACCEs. More evidence is needed to validate our findings.
