Commentary: Use of BACTRAC Proteomic Database-Uromodulin Protein Expression During Ischemic Stroke

Gabriella-Salome K Armstrong, Jacqueline A Frank, Christopher J McLouth, Ann Stowe, Jill M Roberts, Amanda L Trout, Justin F Fraser, Keith Pennypacker, Gabriella-Salome K Armstrong, Jacqueline A Frank, Christopher J McLouth, Ann Stowe, Jill M Roberts, Amanda L Trout, Justin F Fraser, Keith Pennypacker

Abstract

Introduction: Uromodulin (UMOD) is a glycoprotein expressed by the epithelial cells of the thick ascending limb of Henle's loop in the kidney. Research has shown that increased uromodulin expression may be associated with lower risk of cardiovascular disease in adults. Utilizing the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683), a continuously enrolling tissue bank, we aimed to examine the associations between serum uromodulin, age, and high BMI (BMI>25) and its relationship to stroke in patients.

Methods: Arterial blood distal and proximal to the thrombus was collected during a thrombectomy procedure using the BACTRAC protocol and sent to Olink (Boston, MA) to determine proteomic expression via proximity extension assay. Uromodulin expression was recorded and analyzed using two tailed T-tests and linear regressions.

Results: The relationship between systemic and intracranial uromodulin, age, high BMI and hypertension were assessed. Systemic and intracranial uromodulin decreased with age (p<0.0001 and r2=0.343, p=0.0416 and r2=0.102) respectively. Systemic uromodulin expression increased with BMI>25 (p=0.014). Presence of hypertension decreased uromodulin's expression systemically (p=0.018) and intracranially (p=0.007).

Conclusions: Uromodulin was increased significantly in overweight patients, decreased significantly in older patients, and decreased in patients with hypertension. The increase in uromodulin in people with high BMI could be a protective reaction of the kidney to worsening conditions that make ischemic stroke more likely, with a goal of delaying dangerous outcomes. The decreased expression of uromodulin in older adults could be associated with the decline of general kidney function that accompanies aging. Hypertension can contribute to an AKI by decreasing perfusion to the kidney, therefore decreasing kidney function and uromodulin production. Further analyses are needed to understand the role of uromodulin following ischemic stroke.

Keywords: Age; Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC); High Body Mass Index (BMI); Ischemic Stroke; Uromodulin protein.

Conflict of interest statement

Conflicts of Interesxt We are disclosing that Drs. Fraser, Stowe and Pennypacker are co-owners of Cerelux, LLC.

Figures

Figure 1a:
Figure 1a:
Uromodulin protein plasma expression is decreased in systemic arterial blood with age (p2=0.343).
Figure 1b:
Figure 1b:
Uromodulin protein plasma expression is decreased in intracranial arterial blood with age (p=0.0416 and r2=0.102).
Figure 2a:
Figure 2a:
Uromodulin protein plasma expression is increased in systemic arterial blood with BMI greater than 25 (p=0.0139).
Figure 2b:
Figure 2b:
Uromodulin protein plasma expression showed no significant change in intracranial arterial blood based on BMI separated as less than 25 and greater than 25.
Figure 3a:
Figure 3a:
Uromodulin protein plasma expression is decreased in systemic arterial blood in patients with hypertension (p=0.018).
Figure 3b:
Figure 3b:
Uromodulin protein plasma expression is decreased in intracranial arterial blood in patients with hypertension (p=0.0066).

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Source: PubMed

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