Platelets modulate leukocyte population composition within perivascular adipose tissue

Authors: CORKEN, ADAM - University Arkansas For Medical Sciences (UAMS); WEINKOPFF, TIFFANY - University Arkansas For Medical Sciences (UAMS); WAHL, ELIZABETH - Arkansas Children'S Nutrition Research Center (ACNC); SIKES, JAMES - Arkansas Children'S Nutrition Research Center (ACNC); THAKALI, KESHARI - University Arkansas For Medical Sciences (UAMS)

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/11/2025
Publication Date: 2/14/2025
Citation: Corken, A., Weinkopff, T., Wahl, E.C., Sikes, J.D., Thakali, K.M. 2025. Platelets modulate leukocyte population composition within perivascular adipose tissue. International Journal of Molecular Sciences. 26(4):1625. https://doi.org/10.3390/ijms26041625.
DOI: https://doi.org/10.3390/ijms26041625

Interpretive Summary: When people become overweight due to poor nutrition there is a high likelihood that they will develop cardiovascular disease (CVD). Having CVD increases one’s chances of experiencing a heart attack or stroke which occurs when small cells in the bloodstream known as platelets form clots that block blood flow to the heart or brain. Normally platelets only form clots to plug holes in blood vessels when a person is injured to limit blood loss but platelets can also shuttle immune cells from the bloodstream to tissues, often to fight infection. With that in mind, we began feeding laboratory mice a poor diet that was high in fat, sugar and salt. In some mice we removed their platelets, while in others we left their platelets alone. We then looked for changes in the immune cell populations in perivascular adipose tissue. We saw that this poor diet had little effect on the immune cells present in perivascular adipose tissue. However when we removed platelets, we saw changes in the immune cells present in perivascular adipose tissue, and the monocyte/macrophage type of immune cell was the most affected. To our knowledge, this is the first time anyone has reported that platelets affect immune cells in perivascular adipose tissue. This is an important discovery that identifies a role for platelets in modifying the the perivascular environment. Our findings bring about many more questions about how the interplay between platelets and nutrition specifically influences perivascular adipose tissue and ultimately cardiovascular health. If we continue to work our way through this initial discovery to learn all the important parts and mechanisms a poor diet uses to change platelets and perivascular adipose tissue then perhaps we can find ways to unlink poor nutrition from heart attacks and strokes. Our findings are an important step in the research journey that could be beneficial to the millions of individuals who suffer from poor nutrition and CVD.

Technical Abstract: Perivascular adipose tissue (PVAT) regulates vascular tone and is composed of adipocytes and several leukocyte subpopulations. Diet can modify PVAT function, as obesogenic diets cause morphological changes to adipocytes and skew leukocyte phenotype leading to PVAT dysregulation and impaired vasoregulation. Of note, platelets, the clot forming cells, also modulate many facets of leukocyte activity such as tissue infiltration and polar-ity. We aimed to determine if platelets regulate the leukocyte populations residing within PVAT. Male C57Bl/6J mice were fed a Western diet (30% kcal sucrose, 40% kcal fat, 8.0% sodium) to develop obesogenic conditions for PVAT leukocyte remodeling. Diet was either administered acutely (2 week) or extended (8 week) to gauge the length of challenge nec-essary for remodeling. Additionally, platelet depletion allowed for the assessment of platelet relevance in PVAT-leukocyte remodeling. Abdominal PVAT (aPVAT) and thoracic PVAT (tPVAT) was then isolated and leukocyte composition evaluated by flow cytometry. Compared to Control, Western diet alone did not significantly impact PVAT leukocyte composition at either diet length. Platelet depletion, independent of diet, significantly disrupted PVAT leukocyte content with monocytes/macrophages most impacted. Furthermore, tPVAT appeared more sensitive to platelet depletion than aPVAT, providing novel evidence of platelet regulation of leukocyte composition within PVAT depots.