Disclaimer: The information provided here is for educational purposes only and is not intended as medical advice. It should not be used to diagnose, treat, cure, or prevent any medical condition. Instead, use it as a starting point for discussion with your healthcare provider. Always consult with a qualified healthcare provider before starting any new medication, supplement, device, or making changes to your health regimen.
MAS-R, MAS receptor, or simply MAS, all refer to the MAS1 receptor. MAS-R is part of the renin-angiotensin system (RAS), which plays a key role in regulating blood pressure, fluid balance, oxidative stress, clotting, and systemic vascular resistance. The MAS1 receptor is activated by angiotensin-(1-7), a peptide hormone created when enzymes like ACE2 cleave a few amino acids off of angiotensinogen derivatives, like angiotensin II. When angiotensin-(1-7) activates MAS-R, it produces effects that oppose the actions of the classic renin-angiotensin system (RAS) by promoting vasodilation, anti-inflammatory, anti-fibrotic, and anti-thrombotic effects. Activation of MAS-R by angiotensin-(1-7) is thus considered to play a protective role in the cardiovascular and renal systems.
Functions of the MAS1 Receptor
MAS-R is an important component of the protective arm of the renin-angiotensin system (RAS). The main ligand for MAS-R is angiotensin-(1-7), a peptide that generally exerts beneficial effects opposing many of the actions of angiotensin II. Here’s a summary of its main functions:
Vasodilation: Activation of MAS-R by angiotensin-(1-7) promotes vasodilation, which can help lower blood pressure and improve blood flow.
Anti-inflammatory Effects: Angiotensin-(1-7) binding to MAS-R has been shown to reduce inflammation in various tissues.
Anti-fibrotic Effects: Activation of MAS-R can also reduce fibrosis in organs such as the heart and kidneys.
Diuresis and Natriuresis: MAS-R activation can promote urine production (diuresis) and sodium excretion (natriuresis), which can help in regulating fluid balance.
Cardioprotection: Through its vasodilatory, anti-inflammatory, and anti-fibrotic effects, MAS-R activation may help protect the heart, particularly after events like myocardial infarction (heart attack).
Protection Against Organ Injury: The effects mediated by MAS-R activation may be protective in various models of organ injury, including the heart, kidneys, and lungs.
Understanding the role of MAS-R and its ligand, angiotensin-(1-7), has led to interest in developing therapeutic strategies that enhance this pathway, especially since it can counteract the often detrimental effects of the classic RAS pathway driven by angiotensin II. Countering the effects of angiotensin II could be of particular importance in conditions where angiotensin II levels are elevated, like POTS (Stewart et al. 2009).
Autoantibodies to MAS1 Receptor
Autoantibodies targeting the MAS1 receptor (MAS-AAbs) have been identified in various studies, indicating an autoimmune component to certain cardiovascular and autonomic dysfunctions. The presence of these autoantibodies seems to be associated with negative chronotropic effects (i.e., slowing down the heart rate). By binding to the receptor, these autoantibodies may alter its normal signaling pathways, potentially disrupting the delicate balance of the renin-angiotensin system and contributing to systemic symptoms. (Bornholz et al. 2017) (Wallukat and Schimke 2014)
Acute COVID-19 and Long COVID
A study by Cabral-Marques and colleagues found that the relationship between autoantibodies targeting G-Protein Coupled Receptors (GPCRs) and RAS-related molecules is associated with the clinical severity of acute COVID-19 infection, suggesting novel molecular pathways for therapeutic interventions for acute COVID-19. (Cabral-Marques et al. 2021)
In the context of Long COVID (LC), functional autoantibodies targeting the MAS receptor, among other G-Protein Coupled Receptors (GPCRs), have been observed. These autoantibodies could potentially interfere with the binding and activation of the receptor by angiotensin-(1-7), which in turn could affect the regulation of the RAS, although the exact implications are not fully elaborated. Another study found significant reductions in the microcapillary density and blood flow through small blood vessels in the retina of the eye for people with LC who had elevated levels of α1-autoantibodies, AT1-autoantibodies, MAS-autoantibodies, and β2-autoantibodies compared to patients without elevated levels of those autoantibodies. Thus, we assume an impact of these GPCR autoantibodies on microcirculation (blood flow through small blood vessels) in LC. (Szewczykowski et al. 2022) (Wallukat et al. 2021)
Post-Cancer Chemotherapy
In one notable case, MAS-AAbs were detected in a patient’s plasma six months after undergoing chemotherapy, alongside several other autoantibodies. This patient suffered from severe gastrointestinal issues like diarrhea, polyneuropathy (nerve damage causing weakness and pain), and unregulated high blood pressure episodes that were mostly triggered by physical or emotional stress. While the direct implications of MAS-AAbs on these specific conditions were not fully specified, their presence highlights how significant medical events, such as chemotherapy, might trigger complex autoimmune responses that affect autonomic function. (Haberland et al. 2013)
Inflammation
While not directly mentioning autoantibodies, a study by Hammer and colleagues explored the critical role of the MAS receptor in counterbalancing angiotensin-II-mediated pro-inflammatory effects. The research highlighted how MAS-R activation specifically affects macrophage function, helping to reduce tissue inflammation. This could suggest that autoantibodies against the MAS receptor might potentially impair these anti-inflammatory pathways, leading to heightened or prolonged inflammatory responses in the body. Although this remains somewhat speculative based on the currently provided information, it opens important avenues for future research into immune dysregulation. (Hammer et al. 2016)
Testing and Resources
While RTHM is no longer offering direct testing, CellTrend will be able to provide information on how you can test today. Visit CellTrend.
Featured image courtesy of Fisher Scientific.
Disclaimer: As always, please consult with a qualified healthcare provider before making any changes to your treatment plan or pursuing new diagnostic testing.