The interplay of endothelial dysfunction, cardiovascular disease, and cancer: What we should know beyond inflammation and oxidative stress
Bibliographic record
Abstract
Dear Editor in Chief of the European Journal of Preventive Cardiology With great enthusiasm, we read the well-conducted study by Toya et al.,1 entitled “Assessment of peripheral endothelial function predicts future risk of solid-tumor cancer”, which was recently published in the European Journal of Preventive Cardiology. It has been well-demonstrated that microvascular dysfunction predicts and predisposes future cardiovascular disease. In the present study, Toya et al. provide us with important data, demonstrating that microvascular endothelial dysfunction, measured by reactive hyperemia peripheral arterial tonometry, signals the increased risk of incident solid-tumor cancer. This study further expands our previously published article,2 raising the issue that cardiovascular disease and cancer not only share modifiable risk factors like diet, sedentary lifestyle, obesity, and tobacco use, but also cellular, signaling, and genetic pathways that are central to the pathogenesis of both diseases. Understanding the significant biological overlap between cardiovascular disease and cancer is crucial and may foster the development of novel therapeutic and preventive strategies for both diseases. Toya et al.1 stated that chronic inflammation and excess oxidative stress are shared underlying biological processes for both atherosclerotic cardiovascular diseases and cancer, and although they could not assess and demonstrate it in the current study, they have justified the link between endothelial dysfunction and incident cancer with these two processes. However, to the best of our knowledge, the interplay of endothelial dysfunction and cancer goes beyond inflammation and excess oxidative stress. As we indicated in our work,2 signaling by the Wnt family of secreted glycolipoproteins plays an important role in the regulation of cell proliferation, polarity, migration, and cell-fate determination. Aberrant Wnt signaling functions are linked to a number of cancers, including prostate, bladder, colon, breast and lymphoma.1 Interestingly, aberrant Wnt signaling plays an important role in promoting endothelial dysfunction and pathogenesis of atherosclerosis.1 Taken together, the Wnt signaling pathway is an emerging biological link between cardiovascular disease, endothelial dysfunction, and cancer, and may be a novel therapeutic target for the joint prevention of both cardiovascular disease and cancer in the future. Another link between endothelial dysfunction, cardiovascular disease, and cancer that has been raised in our article2 is the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR-gamma is a major receptor for the thiazolidinedione class of insulin-sensitizing drugs. In addition to its effect on glucose metabolism and insulin resistance, PPAR-gamma has been shown to improve endothelial dysfunction and reduce atherosclerosis. Interestingly, PPAR-gamma is also expressed in a number of solid tumors, including colon, breast, bladder, lung, and gastric cancers, and acts as a tumor suppressor by reducing proliferation and angiogenesis and promoting differentiation. Moreover, the thiazolidinedione class of PPAR-gamma agonists have been shown to inhibit the Wnt/beta-catenin signaling pathway, which functions in the self-renewal capability of cancer stem cells.2 Cardiovascular disease and cancer are leading causes of mortality and morbidity worldwide, and their incidence is increasing in all socioeconomic classes worldwide. Strategies to improve their treatment and prevention are global priorities and the major focus of the World Health Organization’s joint prevention programs.2 We believe that the findings of Toya et al.1 are very important because the demonstration of a link between endothelial microvascular dysfunction and incident cancer not only helps to distinguish high-risk people for developing cancer and may warrant more attention from healthcare providers to this group of at-risk people, but also further supports the concept of joint pharmacologic prevention of cardiovascular disease and cancer. We thank and congratulate the authors again for their elaborate and illuminating paper.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.017 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.003 |
| Scholarly communication | 0.004 | 0.005 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.033 | 0.040 |
| Insufficient payload (model declined to judge) | 0.005 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".