*For medical professionals only
There is a saying that "disease comes from the mouth", which is true for human beings, but I didn't expect it to be "true" for cells.
Recently, a new study published in the journal Cell Metabolism found that the cause of arteriosclerosis that causes fatal diseases such as pulmonary hypertension (PH) is actually related to the "gluttony" of some cells......
It turns out that in the early stages of the disease, hormones, inflammation, environmental/mechanical stress, and other factors activate the resident pulmonary adventitial fibroblasts (PAAFs), turning PAAFs into "glutamine" targets glutamine and serine, two amino acids that are key raw materials for collagen biosynthesis.
As a result, PAAF has become a major producer of collagen, and the deposition of collagen around the blood vessels promotes arteriosclerosis and leads to diseases such as PH.
The good news is that inhibition of these metabolic pathways, or simply reducing dietary intake of glutamine and serine, is effective in reducing arteriosclerosis and improving cardiovascular function.
This is a big victory for food therapy.
Diagram of the title of the dissertation
Abnormal collagen deposition is one of the direct causes of hardening of the arteries. Collagen is a special type of protein, and the most common motif in its amino acid sequence is glycine-proline-X, or glycine-X-hydroxyproline, where X is any amino acid other than glycine/proline/hydroxyproline.
It is not difficult to see that collagen is particularly rich in glycine, accounting for up to one-third according to relevant research statistics, followed by proline and hydroxyproline can also account for about 20%.
It stands to reason that normal cells simply do not have such a large supply, so the researchers speculate that there must be related metabolic changes in the progression of PH.
After stimulating PAAF with inflammatory factors such as PH-associated IL-6 or mechanical conditions, the researchers observed metabolic shifts, mainly the enrichment of glycine and proline metabolic pathways, as well as the reduction of glutamine and serine in the medium.
Glutamine and serine are the main raw materials for cell biosynthesis of glycine and proline. Apparently, PAAF increases glutamine and serine uptake to synthesize more collagen. The researchers also analyzed the plasma of patients with PH and also observed similar changes in amino acid levels.
Relevant metabolic pathways
Further analysis showed that PAAF metabolic switching was mediated by the YAP/TAZ pathway.
So, can this mechanism be used in reverse to treat PH?
The investigators used inhibitors of proline and glycine biosynthesis-related enzymes, CB-839 and SHIN1, respectively/in combination with the pililine-induced PH rats to reduce the synthesis of the two. The results showed that the inhibition of both could significantly reduce the content of pulmonary vascular collagen and the degree of aortic sclerosis.
INHIBITION OF GLYCINE AND PROLINE BIOSYNTHESIS CAN IMPROVE PH-RELATED PATHOLOGY
When the researchers adjusted the rat diet so that the rat diet was almost free of glutamine and serine, the levels of these two amino acids in the rat's circulation decreased rapidly, and the blood sugar changed significantly. After optimizing the diet, significant improvements in pulmonary vascular collagen content and aortic sclerosis were also observed in PH rats.
Arteriolar myogenesis was also significantly improved
In other words, just changing the diet may also bring good therapeutic effects to PH.
The corresponding author of this paper said in an interview that this is the first time we have found a dietary strategy that can effectively treat PH, providing a new option for lifestyle intervention for PH treatment.
In addition, researchers are also trying to develop new diagnostic methods for PH using PET and glutamine tracing, and by looking for PAAF cells that "glutamine-eaten" can detect PH early, treat it in time, and delay disease progression.
Resources:
[1]https://www.sciencedirect.com/science/article/abs/pii/S155041312400130X?via%3Dihub
[2]https://www.sciencedaily.com/releases/2024/05/240502141221.htm
The author of this article丨 Dai Siyu