Data on the histologic and molecular patterns of vascular remodeling in diabetes are still lacking. In their study, Narayanan et al
1
elegantly compare the arterial response to balloon-mediated carotid injury in diabetic rats with nondiabetic rats and provide a pathophysiologic and transcriptomic database for differences in vascular response without and with insulin resistance. They successfully apply novel bioinformatics tools in this established model of arterial injury to analyze gene expression and regulation associated with balloon injury. The authors' work is relevant, impactful, and timely. Diabetes mellitus constitutes a global health burden. The results of the National Health and Nutrition Examination Survey show that the prevalence of diabetes has nearly doubled over the last three decades.2
This pervasive disease often presents with unique patterns of peripheral atherosclerosis.3
The outcomes of percutaneous intervention in this group have heretofore seemed worse than in nondiabetic patients.4
In an era where the number of endovascular interventions performed has increased continually, understanding the arterial response to treatment delivery and minimizing negative vascular remodeling are of the utmost importance to guide future therapeutic advances.5
This article shows the mechanisms underlying the distinct and inferior outcomes of endovascular revascularization in this high-risk population. In a simulated percutaneous transluminal angioplasty model consisting of Fogarty balloon arterial stretch, insulin-resistant type 2 diabetic rats showed significantly greater neointimal thickness driven by increased numbers of contractile smooth muscle cells and an aberrant inflammatory response. Goto-Kakizaki rats exhibited sustained upregulation of smooth muscle cell proliferation genes for ≤6 weeks after injury.
To date, treatment algorithms are rarely based on phenotypes of vascular response, limiting the application of personalized medicine. Strides in endoluminal device development have been made in parallel with but not in conjunction with the steadfast discovery of molecular markers of intimal response.
6
Therapeutic targeting of vascular growth and remodeling modifiers is long awaited. This work establishes a rich database of gene expression associated with arterial healing and has the potential to serve as the cornerstone for personalized vascular medicine. The optimal endovascular treatment for symptomatic peripheral arterial occlusive disease could combine not only a mechanical solution for a sustained hemodynamic treatment, but also a biologic therapy targeting patient-specific vascular healing pathways.To decrease postintervention neointimal hyperplasia and its sequela restenosis, drug-coated balloons and drug-coated and -eluting stents are commonly used in contemporary practice. In this study, the authors used a conventional balloon-mediated injury that is a closer model for plain old balloon angioplasty. Future studies may, thus, include this important variable.
In summary, this study provides granular animal data on the delayed vascular healing associated with diabetes after endovascular intervention. Additional translational science is needed to further understand the diabetic arterial response to the vast array of available endovascular therapies and help to guide treatment selection as well as potentially target vascular remodeling on a molecular level. Clinicians know that a one-size-fits-all endovascular treatment protocol is insufficient; the long-term durability of peripheral endovascular intervention may require the application of transcriptomics to target patient-specific mechanisms of vascular response after revascularization.
The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery Cases and Innovative Techniques or the Society for Vascular Surgery.
References
al ARe. Transcriptomic and physiological analyses reveal temporal changes contributing to the delayed healing response to arterial injury in diabetic rats. J Vasc Surg Vasc Sci 20XX, 1, XX-XX doi: XXXX.
- Prevalence trends of diabetes subgroups in the United States: a data-driven analysis spanning three decades from NHANES (1988-2018).J Clin Endocrinol Metab. 2022; 107: 735-742
- A review of distribution of atherosclerosis in the lower limb arteries of patients with diabetes mellitus and peripheral vascular disease.Vasc Endovascular Surg. 2018; 52: 535-542
- Diabetes and atherosclerosis: epidemiology, pathophysiology, and management.JAMA. 2002; 287: 2570-2581
- National trends in lower extremity bypass surgery, endovascular interventions, and major amputations.J Vasc Surg. 2009; 50: 54-60
- Targeting smooth muscle cell phenotypic switching in vascular disease.JVS Vasc Sci. 2021; 2: 79-94
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Published online: May 08, 2023
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Author conflict of interest: none.
The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest.
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- Transcriptomic and physiological analyses reveal temporal changes contributing to the delayed healing response to arterial injury in diabetic ratsJVS-Vascular Science
- PreviewAtherosclerosis is a leading cause of mortality in the rapidly growing population with diabetes mellitus. Vascular interventions in diabetic patients can lead to complications attributed to defective vascular remodeling and impaired healing response in the vessel wall. In this study, we aim to elucidate the molecular differences in the vascular healing response over time using a rat model of arterial injury applied to healthy and diabetic conditions.
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