Allo-HSCT is a life-saving therapy for many malignant and non-malignant blood disorders. However, patients undergoing this treatment are at risk of developing graft-versus-host disease (GvHD) and face a significantly higher incidence of cardiovascular events later in life. Until now, it remained unclear whether allo-HSCT itself could directly promote atherosclerosis, the underlying cause of most cardiovascular disease.

The study led by Ivana Jorgacevic, Haroon Shaikh, Andreas Beilhack and Alma Zernecke was recently published in Cardiovascular Research, a leading journal in Cardiovascular Research.

In a newly developed experimental mouse model, researchers demonstrated that allo-HSCT can indeed exacerbate atherosclerotic plaque formation. Researchers demonstrated that allo-HSCT can indeed exacerbate atherosclerotic plaque formation. Using mice that develop atherosclerosis because they can’t clear “bad” cholesterol, the team compared outcomes between mice groups receiving bone marrow alone and those receiving bone marrow plus MHC minor-mismatched donor T cells.

Mice receiving allogeneic bone marrow and T cells developed significantly larger atherosclerotic lesions compared with control groups. These lesions showed increased infiltration of killer T cells within the aorta. Transplanted mice also showed higher serum cholesterol levels, a key risk factor for cardiovascular disease. Importantly, depletion of killer T cells reduced both atherosclerotic plaque burden and cholesterol levels.

Despite only mild clinical signs of GvHD and low disease activity in classical target organs, the cardiovascular events were pronounced, highlighting a previously underappreciated consequence of allo-HSCT.

Cardiovascular disease is a leading cause of late morbidity and mortality among allo-HSCT survivors, who face more than double the risk of premature cardiovascular death compared with the general population. This study provides a mechanistic link between allo-HSCT, immune-mediated inflammation, and accelerated atherosclerosis.

 

“Our findings suggest that donor-derived CD8⁺ T cells play a central role in driving vascular inflammation and lipid dysregulation after transplantation,” the authors note. “Targeting these immune pathways may offer new strategies to reduce long-term cardiovascular complications in allo-HSCT patients” say Andreas Beilhack and Alma Zernecke.

“The study strengthens the rationale for more nuanced cardiovascular risk stratification after allo-HSCT, indicating that transplant-related immune factors—rather than traditional risk markers alone—may help identify patients who warrant earlier surveillance and targeted preventive strategies, even when GvHD appears clinically mild” emphasizes Haroon Shaikh.

The results identify CD8⁺ T cells as a potential therapeutic target to mitigate GvHD-associated cardiovascular disease without compromising the life-saving benefits of allo-HSCT. Future studies will be needed to determine how these findings translate to patients and whether immune-modulating approaches can safely reduce cardiovascular risk in clinical settings.

 

Read the full article in Cardiovascular Research:

https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvaf229/8326789?login=false

 

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