Serial measures of microparticles during intense physical activity in untrained subjects with different endothelial abnormalities: new useful biomarkers for individual evaluation?

Diffuse utilisation of microparticles produced by the endothelium, platelets, leukocytes and monocytes recently made a detailed and precise estimation of the endothelial dysfunction possible: this effect is modulated by the level of apoptosis and pro-coagulation state, as well as by the endothelial reconstruction with progenitor cells. Cell apoptosis is commonly associated with conformational changes of the plasma membrane, condensation of the nucleus, followed by DNA fragmentation and the release of submicroscopic membranous particles. Circulating microparticles of endothelial origin are both markers and triggers of endothelial dysfunction in cardiovascular diseases, and have a possible role as additional indicators of risk as well as possible prognostic markers.¹ However, to be released, modifications in cell structural architecture involving the disruption of cytoskeleton protein organisation must occur.

It seems that the level of microparticles varies on a very wide spectrum of risk profile, from low risk to high risk, from stable coronary artery disease (CAD) to the unstable acute coronary syndrome.² In patients with CAD on 6 years follow-up (MACCE study) the number of microparticles is related to the occurrence of major events, demonstrating a prognostic value;³ microparticles increase the predictive value as added to the Framingham risk estimation, similarly to pro-brain natriuretic peptide (pro-BNP) or to high sensitivity C-reactive protein (hsCRP). An interaction between microparticles and hsCRP has been demonstrated. It has been proved that microparticle release is also related to the level of glucose control, being higher in patients with pre-diabetes as well as in patients with diabetes, compared to individuals with normal glucose control.⁴ Unfortunately, the method is not yet standardised; it is utilised on a small sample sizes and not for clinical and prognostic stratification on a large sample size with randomised studies.

Moderate use of exercise is well known as being effective in the long term to reduce cardiovascular risk;⁵ it stabilises or even reverses atherosclerosis progression in some districts in different cardiovascular diseases and reduces markers of inflammation and oxidative stress, including in patients with a high-risk profile. Moderate physical activity seems more effective in trained than in untrained individuals for better adaptation to pro-coagulant and pro-inflammatory stress. Another mechanism of adaptation might be a more rapid clearance of microparticles from the circulation: chronic exercise, including of high intensity, in professional runners does not modify microparticle release and increases progenitor cells demonstrating that it is useful and not dangerous.⁶ The efficacy of strenuous or very prolonged exercise is still debated. In particular, it has already been demonstrated that several markers of myocardial strain and injury, such as pro-BNP and high-sensitivity troponin T, as well as markers of vascular inflammation and thrombocyte activation, are transiently increased acutely after a marathon. We still do not know if intensive and prolonged exercise, such as a marathon, is harmless or not.

A recent interesting article published in European Journal of Preventive Cardiology has shown in healthy subjects, that a marathon is able to increase microparticle release, produced by the endothelium, plasma cells, leukocytes and monocytes, returning to baseline two days after the race.

Few long-term studies have evaluated the changes in microparticles after different treatments: one study demonstrated that microparticles are specifically increased in peripartum cardiomyopathy, in which a disruption of endothelial integrity has been demonstrated, and are consistently reduced after effective treatment using bromocriptine.⁸

Another study⁹ demonstrated that the effectiveness of stopping smoking is very different between healthy smokers and patients with chronic obstructive pulmonary disease: in the first category, microparticles decreased in the long term; in the second category, stopping smoking has no effect on microparticle number because the anatomical alteration of endothelium is irreversible. It has been postulated¹⁰ that microparticles are potential biomarkers for severity in or contribute to the pathogenesis of pulmonary hypertension. They are potentially useful for the early recognition of the abnormality of vascular endothelium, detecting damage before symptoms occur.

In recent years, there has been a wide range of different categories of individuals performing marathons, including people with risk factors, people with impaired glucose tolerance, diabetes, people with a high-risk profile or stable CAD: these all have different levels of microparticle increase. It would be very interesting to evaluate these markers in one or several categories to test whether the increase in microparticles is transient or permanent, together with T troponin and hsCRP: the results of these studies could provide more in-depth understanding of whether marathons are useful or harmful in these categories of patients, in whom endothelial dysfunction is already present, to different degrees. It could be speculated that the effect of intense physical exercise is different depending on the state of the endothelium before the race. Another possibly interesting point to elucidate is the effect of moderate and very intense exercise, such as a marathon, not only in the short term but also in the long term, because atherosclerosis occurs and evolves over a long period of time and the long-term effects of a transient increase in microparticles are still unknown. If microparticles can successfully help to monitor the state of the endothelium, they could be useful to estimate individually the effects of intense physical exercise.

Declaration of conflicting interests

The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author received no financial support for the research, authorship, and/or publication of this article.

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