In honor of my recent nomination, acceptance, and initiation as Full Membership in Sigma Xi The Scientific Research Honor Society that is the world’s largest multidisciplinary honor society for scientists and engineers, this week’s FB posts will be dedicated to recent scientific discoveries along the #lohcurve.
Three years ago, in September 2020, I did a video presentation at the invitation of SVHI titled “Ancient Molecules for Health Hearts” where I explained why melatonin is important during and after an infection by THE virus because of the various mechanisms used by the virus that can potentially cause heart damage[1].
Three years later, the relevance of heart health post-C infection is starting to gain prominence in the scientific/research community. Many studies have since reported associations between C19 and cardiovascular manifestation discussed in my video presentation, including myocarditis or myopericarditis, cardiomyopathy, arrhythmias due to pulmonary embolism, or even endocarditis [2].
It is now understood that post-acute cardiovascular complications are quite common after viral infections, especially for patients with pre-existing cardiovascular risk factors and chronic diseases. What is most important is that In comparison to patients without a history of C19 infections, those with an acute COVID-19 infection showed a higher risk for various types of cardiovascular complications, including de novo arrhythmias, ischemic heart diseases, or thromboembolic events after one year [3].
Unfortunately, affected individuals and healthcare providers may not associate these new complications with a previous acute viral infection that happened more than one year ago. In that sense, it renders the approach and options to dealing with these complications to become even more challenging because the cause may not be correctly identified.
For example, the case of delayed myocardial injuries in athletes can be a major concern because athletes are most susceptible to cardiovascular complication such as myocarditis or a pre-myocardial injury that can remain silent for a long time post viral infection. Athletes as a result of the strenuous demands from their profession, may have increased arterial stiffness and decreased vascular function that can potentially exacerbate myocardial inflammation that can cause cardiac injuries [4-7].
What is most important, is the revelation that there exists a definitive, tight correlation between #longcovid (PASC) and the risk of developing heart failure.
A recent peer-reviewed study involving patients infected by THE virus found marked elevated risk of developing heart failure after an acute infection. These patients were found to have a 69% higher unadjusted risk of developing heart failure and the risk remained elevated at 45% even after adjusting for age, risk factors, or race/ethnicity.
At this point, I am sure you are impatiently waiting for me to explain the association between melatonin, phase separation, and the attenuation of myocardial injuries that may be induced by viral infections.
In the Sept 2020 video, I talked about how THE virus causes fragmentation in sarcomeres in cardiomyocytes (see image below). Sarcomeres are the basic contractile units of cardiomyocytes and damage to sarcomeres can cause a variety of cardiac dysfunctions because sarcomeres work by having thin (actin) and thick (myosin) filaments that slide past each other during contraction. However, the mechanical force generated by sarcomere actin and myosin requires stabilization by an anchoring structure. Without this anchoring structure, sarcomere units cannot contract properly, and you can end up with different cardiac dysfunctions.
Not surprisingly, this anchoring structure is dependent upon phase separation, and we all know that THE virus can interfere and hijacks host phase separation processes [9].
When sarcomeres are damaged or require replacement, the body must assemble new, functional units. During sarcomere biogenesis, various proteins acting like membraneless condensates will start to grow in size and fuse together via phase separation processes.
In my April video presentation with Jay Campbell, I talked about the role of scaffolds and clients in phase separation. During sarcomere biogenesis, a protein called FATZ-1 acts like a scaffold to attract and help incorporate the client protein α-actinin-2 to form membraneless biomolecular condensates called Z-bodies that are required as foundation building blocks for sarcomere assembly [10]. Thus it is possible that THE virus not only causes fragmentation of sarcomeres, but also prevents new sarcomeres from being synthesized by preventing proper phase separation.
There is no doubt in my mind that the ability of melatonin to regulate phase separation helps the body to rebuild sarcomeres quickly during acute viral infections to protect the heart.
The more you know, the more powerful you are. Got MEL?
References:
[1] https://www.youtube.com/watch?v=JsO-XlUHsV0&feature=emb_logo
[2] Luchian, M.-L.; Demeure, F.; Higny, J.; Berners, Y.; Henry, J.; Guedes, A.; Laurence, G.; Saidane, L.; Höcher, A.; Roosens, B.; et al. Three Years of COVID-19 Pandemic—Is the Heart Skipping a Beat? COVID 2023, 3, 715–727.
[3] Xie, Y.; Xu, E.; Bowe, B.; Al-Aly, Z. Long-term cardiovascular outcomes of COVID-19. Nat. Med. 2022, 28, 583–590.
[4] Brawner, C.A.; Ehrman, J.K.; Bole, S.; Kerrigan, D.J.; Parikh, S.S.; Lewis, B.K.; Gindi, R.M.; Keteyian, C.; Abdul-Nour, K.; Keteyian, S.J. Inverse Relationship of Maximal Exercise Capacity to Hospitalization Secondary to Coronavirus Disease 2019. Mayo Clin. Proc. 2021, 96, 32–39.
[5] Zbinden-Foncea, H.; Francaux, M.; Deldicque, L.; Hawley, J.A. Does High Cardiorespiratory Fitness Confer Some Protection Against Proinflammatory Responses After Infection by SARS-CoV-2? Obesity 2020, 28, 1378–1381.
[6] Bauer, P.; Kraushaar, L.; Dörr, O.; Keranov, S.; Nef, H.; Hamm, C.W.; Most, A. Vascular alterations among male elite athletes recovering from SARS-CoV-2 infection. Sci. Rep. 2022, 12, 8655.
[7] Alosaimi, B.; AlFayyad, I.; Alshuaibi, S.; Almutairi, G.; Alshaebi, N.; Alayyaf, A.; Alturaiki, W.; Shah, M.A. Cardiovascular complications and outcomes among athletes with COVID-19 disease: A systematic review. BMC Sports Sci. Med. Rehabil. 2022, 14, 74.
[8] Salah, H.M.; Fudim, M.; O’neil, S.T.; Manna, A.; Chute, C.G.; Caughey, M.C. Post-recovery COVID-19 and incident heart failure in the National COVID Cohort Collaborative (N3C) study. Nat. Commun. 2022, 13, 4117.
[9] Loh, D.; Reiter, R. J. Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19. Int. J. Mol. Sci. 2022, 23 (15), 8122. https://doi.org/10.3390/ijms23158122.
[10] Sponga, A.; Arolas, J. L.; Schwarz, T. C.; Jeffries, C. M.; Rodriguez Chamorro, A.; Kostan, J.; Ghisleni, A.; Drepper, F.; Polyansky, A.; De Almeida Ribeiro, E.; et al. Order from Disorder in the Sarcomere: FATZ Forms a Fuzzy but Tight Complex and Phase-Separated Condensates with α-Actinin. Sci Adv 2021, 7.
GreatCosmicMothersUnite 