Erectile Dysfunction
Figure 1: Ageing and Vascular Risk Factors Alter Endothelial Repair Capability by Hampering Local Angiogenesis and Systemic Vasculogenesis
Increase in vascular regenerative capacity by improving EPC-driven vasculogenisis, thus reducing EDys, atherosclerosis, ED and CVD
Increase
Biological functions Re-endothelisation capacity
Angiogenesis Atherosclerosis
Decrease Mobilisation Viability
Differentiation Angiogenic capability EDys Atherosclerosis ED CVD
Impairment in these events is associated with endothelial dysfunction (EDys), atherosclerosis, erectile dysfunction (ED) and cardiovasular disease (CVD). Vasculoprotective actions increase neighbouring endothelial activation and in particular endothelial progenitor cell (EPC) functions, improving endothelial function and preventing the progression of EDys, atherosclerosis, ED and CVD. PDE51 = phosphodiesterase type 5 inhibitors; VRFs = vascular risk factors. Adapted from Costa and Vendeira 2007117
and Costa 2009.71 modifications in the arrangement of elastic fibres.54,55 Allied
to its essential effects on vascular function, the cellular and molecular impairment on these components will have an effect on erectile function.56
Ageing-associated Alterations in Vascular Repair Mechanisms
EDys and vascular injury represent the imbalance between endothelial damage and endogenous recovery.16
mechanisms of angiogenesis and adult vasculogenesis are usually activated to regenerate the affected EC monolayer. The angiogenic process refers to the proliferation and migration of adjacent ECs to injured sites, which repairs them.57
During post-natal vasculogenesis,
endothelial progenitor cells (EPCs) are mobilised from the bone marrow to neovascular sites, where they differentiate into mature ECs, integrating and re-generating disrupted endothelium.58
The
progression of age and the co-existence of VRFs was reported to deregulate angiogenesis and vasculogenesis mechanisms, preventing endothelial monolayer integrity and sustaining and exacerbating EDys, with consequent effects on erectile and cardiovascular function (see Figure 1).
Angiogenesis and Ageing
With the progression of age, local angiogenic function is progressively impaired and has therefore been linked to the increased risk of vascular disease in geriatric men.59
With ageing, angiogenesis
becomes altered as result of several impairments in the local neovascular response such as deregulation in growth factor expression, ECM and inflammatory modifications and reduced eNO bioavailability.60,61
Evaluation, Management, Prevention and Treatment of Erectile Dysfunction in Elderly Men
Evaluation of Endothelial Dysfunction in Aged Men with Erectile Dysfunction
When assessing ED in the elderly it can never be over-stressed that EDys and atherosclerosis are systemic conditions affecting both the penile and coronary arteries.20
For this reason ED is now considered to
be a marker of clinically undiagnosed vascular systemic disorder,26 revealing an increased risk for cardiovascular events.78
The underlying
EDys state damaging both penile and other vascular beds may be measured systemically as impaired vasodilation of the brachial artery and is of prognostic value for cardiovascular events, such as myocardial infarction or stroke.79
In fact, the cardiovascular system
The additional presence of VRFs with age and the increased OS synergistically hamper these mechanisms, further exacerbating EDys conditions. In ageing ED, molecular therapies with VEGF and eNO were reported to have beneficial effects on cavernosal endothelial and erectile function.27,62
These vascular mediators may
transiently potentiate angiogenesis mechanisms and improve local endothelial repair capability. However, mature ECs possess limited regenerative capacity, which with ageing becomes even more restricted. For this reason, most research is currently focused on
46
patients with cardiovascular disease and ED are stratified according to three risk levels based on their cardiovascular risk. The low-risk category includes patients to whom sexual activity does not represent a significant cardiac risk. The intermediate category includes patients who require further testing before resuming sexual activity. The high-risk category consists of patients whose cardiac conditions are severe or unstable and to whom sexual activity may pose a significant threat. These patients, who are often moderately or severely symptomatic, should be referred for cardiological evaluation.
should also be assessed before initiating any treatment for ED. According to the second Princeton Consensus Conference guidelines,80
EUROPEAN UROLOGICAL REVIEW Vascular repair
Ageing VRFs
Vasculogenesis EPCs
Vasculoprotective effects:
• Exercise
• Healthy eating habits • PDE51 • Testosterone
vasculogenesis and the role of immature EPCs, both as a marker of EDys and as a basis for vascular regenerative therapy.
Vasculogenesis and Age Progression
Ageing was associated with a reduction in the number of circulating EPCs (cEPCs) in patients with ED and CVD.66,67 Furthermore, the progressive decrease of cEPCs correlated with the severity of cavernous artery atherosclerosis.68
The additional chronic
exposure to VRFs and associated increased OS are accountable for affecting EPC mobilisation, homing, differentiation and integration in injured vascular sites.69–71
alteration of constitutive human telomerase activity can also affect the regenerative capacity of EPCs, thus hampering the ability of EPCs to respond to the adequate stimuli.75
Age-related reduced levels of angiogenic
and mobilising cytokines such as VEGF and eNO also impair EPC mobilisation, migration, proliferation and survival.72–74
In addition, the In the elderly, alterations in
vasculogenesis systemic response may also result from the accelerated senescence and apoptosis as well as an age-associated exhaustion of the pool of available EPCs in the bone marrow.16,73,76,77
All
of these alterations may reveal the extent of EDys in the aged individual, potentiating atherosclerosis, ED and CVD. Highlighting the relevance of the vasculogenesis process, it has been reported that EPC functions, endothelial health and erectile function may be improved by ED therapeutic strategies, as discussed further in the next section. Currently, the evaluation of cEPCs remains a a research tool; however, it is crucial to assess and manage the status of penile and systemic EDys using the available techniques in the geriatric patient with ED, thus preventing cardiovascular events.
The ageing of EPCs is considered to be a central player in the decline of endothelial repair mechanisms, vascular function and organ integrity in the elderly. A reduction in EPCs in the peripheral circulation may be regarded as a sign of systemic EDys. With ageing, the bioavailability and most of EPC-driven biological roles are altered, thus impairing vasculogenesis and endogenous endothelial regeneration.63–65
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