Abstract:
:The rates of erectile dysfunction (ED) in heart failure (HF) are extremely high. Limited capacity of patients with HF to exercise and coronary artery disease are considered to be the main causative mechanisms. Both HF and ED are associated with increased levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL- 8). The increased levels of proinflammatory cytokines in ED suggest that inflammatory markers act as important active agents in ED development. The innate immune system also reacts to danger signals released by damaged cells. Damage-associated molecular patterns (DAMPs) are molecules released as a result of tissue injury acting on immune activation during non-infectious inflammation. DAMPs may also reach the circulation and mediate pathophysiological processes that occur in distant organs to the injured site. Cardiomyocytes possess abundant mitochondria and during tissue damage, it is likely that the heart releases high amounts of mitochondrial DNA (mtDNA), which acts as a potent ligand for Toll-like receptor 9 (TLR9). Accordingly, in the present manuscript we review the literature pertaining the relationship between HF and ED and the subjacent inflammatory process associated to both diseases. In addition, we propose the hypothesis that TLR9 activation by DAMPs released in HF leads to inflammation, vascular dysfunction and functional changes in cavernosal tissue, providing an additional mechanism that connects HF to ED. Since TNF-α usually is a product of TLRs activation and seems to be a common link between HF and ED, our hypothesis provide two possible targets to treat the ED associated to HF and may have important preventative and therapeutic implications.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Rodrigues FL,Fais RS,Tostes RC,Carneiro FSdoi
10.2174/1389450116666150420145757subject
Has Abstractpub_date
2015-01-01 00:00:00pages
442-50issue
5eissn
1389-4501issn
1873-5592pii
CDT-EPUB-66668journal_volume
16pub_type
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