# Immune response in dogs with myxomatous mitral valve disease: insights into monocyte and lymphocyte subtypes and natural killer cells

**Authors:** Martina Cimerman, Alenka Nemec Svete, Anže Baš, Melita Hajdinjak, Miha Bajc, Sara Petek, Katka Pohar, Alojz Ihan, Uroš Krapež, Branko Krt, Klemen Dolinar, Katarina Miš, Sergej Pirkmajer, Aleksandra Domanjko Petrič

PMC · DOI: 10.1093/jvimsj/aalag028 · Journal of Veterinary Internal Medicine · 2026-02-25

## TL;DR

This study explores immune changes in dogs with heart disease, focusing on monocytes, T cells, and cytokines at different disease stages.

## Contribution

The study identifies immune cell and cytokine changes in dogs with MMVD at various disease stages, suggesting a role for inflammation.

## Key findings

- Monocyte percentages were higher in dogs with congestive heart failure compared to preclinical stages.
- Activated T helper lymphocytes were lower in compensated heart failure compared to other groups.
- Proinflammatory cytokine concentrations increased in advanced disease stages.

## Abstract

The immune response in dogs with myxomatous mitral valve disease (MMVD) is understudied.

Investigate the populations of monocyte subtypes, natural killer cells (NK cells), and T lymphocyte subtypes in dogs with MMVD and their relationships with selected cytokines and echocardiographic parameters at different stages of the disease and in comparison to healthy dogs.

Eighty-one client-owned dogs: 64 with MMVD (preclinical stage, compensated congestive heart failure [CHF], decompensated CHF) and 17 healthy dogs.

Cross-sectional study. Natural killer (NK) cells, monocyte subtypes, T lymphocyte subtypes, and B lymphocytes were identified using flow cytometry. Generalized linear models were used to compare variables between groups. Pairwise comparisons were performed using estimated marginal means with Tukey correction. P-value < .05 was considered significant.

The percentage of monocytes was higher in dogs with compensated and decompensated CHF compared with preclinical dogs. The percentage of activated T helper lymphocytes was lower in compensated CHF compared with all other groups. No differences in percentages were found for monocyte subtypes, NK cells, cytotoxic, regulatory and double positive T lymphocytes, or B lymphocytes. Concentration of monocyte chemoattractant protein-1 was higher in the decompensated CHF compared with all other groups, and the concentration of keratinocyte chemotactic-like chemokine was higher in the decompensated CHF compared with the preclinical group.

Higher concentrations and percentages of total monocytes and concentrations of proinflammatory cytokines in CHF suggest an inflammatory pathway in MMVD progression. Activated T helper lymphocytes may be downregulated in dogs with compensated CHF.

## Linked entities

- **Diseases:** congestive heart failure (MONDO:0005009)

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 403931], APC (APC regulator of WNT signaling pathway) [NCBI Gene 479139], PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 490255] {aka CD45}, IL1B (interleukin 1 beta) [NCBI Gene 403974] {aka IL-1}, CRP (C-reactive protein) [NCBI Gene 488629], FOXP3 (forkhead box P3) [NCBI Gene 491876], IL6 (interleukin 6) [NCBI Gene 403985] {aka IL-6}, CD5 (CD5 molecule) [NCBI Gene 612338], CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, TNF (tumor necrosis factor) [NCBI Gene 403922] {aka TNFA, TNLG1F, cTNF}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 403870] {aka CD25, IL-2RA}, CAT (catalase) [NCBI Gene 403474], LOC479668 (haptoglobin-like) [NCBI Gene 479668] {aka HP, HPR}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 403981], CD14 (CD14 molecule) [NCBI Gene 607076], IL10 (interleukin 10) [NCBI Gene 403628] {aka IL-10}, IL2 (interleukin 2) [NCBI Gene 403989], IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, REN (renin) [NCBI Gene 403838], FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}
- **Diseases:** tachypnea (MESH:D059246), heart murmur (MESH:D006337), ischemic heart disease (MESH:D017202), cardiovascular disease (MESH:D002318), neutrophilia (MESH:C563010), death (MESH:D003643), tissue injury (MESH:D017695), heart disease (MESH:D006331), cardiac remodeling (MESH:D020257), ACVIM (MESH:D000034), tricuspid regurgitation (MESH:D014262), CHF (MESH:D006333), cardiogenic pulmonary edema (MESH:D011654), dyspnea (MESH:D004417), MMVD (MESH:C564326), cardiac fibrosis (MESH:D005355), NLR (MESH:D015467), cardiac inflammation (MESH:D007249), myocarditis (MESH:D009205), tachycardia (MESH:D013610), autoimmune conditions (MESH:D001327)
- **Chemicals:** furosemide (MESH:D005665), Alexa Fluor 647 (MESH:C569686), A9418 (-), formaldehyde (MESH:D005557), amlodipine (MESH:D017311), PBS (MESH:D007854), DPT (MESH:C059372), DNT (MESH:C023514), spironolactone (MESH:D013148), torsemide (MESH:D000077786), aldosterone (MESH:D000450), potassium dihydrogen phosphate (MESH:C013216), pimobendan (MESH:C041648), sodium chloride (MESH:D012965)
- **Species:** Homo sapiens (human, species) [taxon 9606], Canis lupus familiaris (dog, subspecies) [taxon 9615], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** 0112 — Homo sapiens (Human), Transformed cell line (CVCL_K381), 82 — Homo sapiens (Human), Xeroderma pigmentosum, complementation group A, Finite cell line (CVCL_L495), MA516605 — Mus musculus (Mouse), Hybridoma (CVCL_J838)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12935012/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12935012/full.md

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Source: https://tomesphere.com/paper/PMC12935012