Just a few minutes ago I did a post on the causative role of estrogen and its metabolites in both rheumatoid (RA) and osteo arthritis (OA). The study below presents evidence that a C-16 hydroxylated metabolites of estrogen is a causative factor in the progressive and invariably lethal condition known as PAH. Now, there is already strong evidence implicating serotonin (5-HT) as one of the causative factors in PAH and due to the accumulation of such evidence Pfizer is running clinical trials with a 5-HT antagonist known as terguride for treating PAH (and also heart failure). Considering estrogen and serotonin go hand in hand (both promote each other’s synthesis), the study below should not come as a surprise to anybody, and it actually suggests an additional pathway to target for patients with PAH who do not respond to a treatment with a 5-HT blocker – i.e. inhibiting estrogen synthesis and its activity at the receptor level, and improving mitochondrial function. Why the latter? Well, because the study found that the estrogenic metabolite drives PAH pathology by inhibiting mitochondrial function. This anti-mitochondrial finding in regards to estrogen is just (if not more) damning as the findings discussed previously that estrogen is genotoxic, mutagenic carcinogen. Thus, in addition to the obvious anti-estrogenic remedies such as vitamin E, progesterone, androgens, aspirin, and so on one can also add niacinamide, methylene blue, vitamin K, thyroid, and other substances which have a pro-metabolic/pro-mitochondrial effect(s).
https://doi.org/10.1161/CIRCULATIONAHA.115.016133
“…MicroRNA array profiling of human lung tissue found elevation of microRNAs associated with energy metabolism, including the miR-29 family, among HPAH patients. miR-29 expression was 2-fold higher in Bmpr2 mutant mice lungs at baseline compared with controls and 4 to 8-fold higher in Bmpr2 mice exposed to 16α-hydroxyestrone (16αOHE) 1.25 μg/h for 4 weeks. Blot analyses of Bmpr2 mouse lung protein showed significant reductions in peroxisome proliferator–activated receptor-γ and CD36 in those mice exposed to 16αOHE and protein derived from HPAH lungs compared with controls. Bmpr2 mice treated with anti–miR-29 (20-mg/kg injections for 6 weeks) had improvements in hemodynamic profile, histology, and markers of dysregulated energy metabolism compared with controls. Pulmonary artery smooth muscle cells derived from Bmpr2 murine lungs demonstrated mitochondrial abnormalities, which improved with anti–miR-29 transfection in vitro; endothelial-like cells derived from HPAH patient induced pluripotent stem cell lines were similar and improved with anti–miR-29 treatment.”
“…16αOHE promotes the development of HPAH via upregulation of miR-29, which alters molecular and functional indexes of energy metabolism. Antagonism of miR-29 improves in vivo and in vitro features of HPAH and reveals a possible novel therapeutic target.”
