bims-minfam 2025-08-31 papers

Issue of 2025–08–31
eight papers selected by
Ayesh Seneviratne, McMaster University

JACC CardioOncol. 2025 Aug;pii: S2666-0873(25)00249-2. [Epub ahead of print]7(5): 470-495

Clonal Hematopoiesis in Cancer and Cardiovascular Disease: JACC: CardioOncology State-of-the-Art Review.

Emerging evidence suggests a dynamic relationship exists between cancer and cardiovascular disease (CVD). CVD is common among cancer survivors; however, it also may increase the risk of developing cancer. The underlying factors driving this connection remain poorly understood. Aging, chronic inflammation, and perturbed immune signaling are shared hallmarks of cancer and CVD. Clonal hematopoiesis (CH), the age-related accumulation of somatic mutations in hematopoietic cells leading to cells with a growth advantage, is associated with immune dysregulation in elderly people. Growing evidence suggests that CH is a risk factor for CVD. Although the link between CH and hematological cancer is well established, its relationship to solid organ cancers is far less understood. This review provides an in-depth analysis of the evidence linking CH with solid organ malignancies and explores its role as a shared risk factor for the development of both CVD and cancer. Furthermore, it discusses the potential mechanisms by which CH may contribute to CVD among cancer survivors.

Keywords: CHIP; LOY; cardiomyopathy; cardiotoxicity; coronary artery disease; heart failure; mCAs; solid organ tumors; therapy-related clonal hematopoiesis

DOI: https://doi.org/10.1016/j.jaccao.2025.06.006

JACC CardioOncol. 2025 Aug;pii: S2666-0873(25)00244-3. [Epub ahead of print]7(5): 496-500

Managing Cardiovascular Risk in Clonal Hematopoiesis of Indeterminate Potential: JACC: CardioOncology Short-Form Primer.

Ohad Oren, Aeron M Small, Amy E Lin, Peter Libby.

Keywords: CHIP; CHIP clinic; coronary artery disease; leukemia; prevention; risk prediction

DOI: https://doi.org/10.1016/j.jaccao.2025.05.013

J Am Coll Cardiol. 2025 Aug 22. pii: S0735-1097(25)07388-7. [Epub ahead of print]

Clonal Hematopoiesis and Cardiovascular Outcomes in Older Women.

Daniel Ezzat, Md Mesbah Uddin, Liying Xue, Yash Pershad, Shengruo Zhang, Jason M Collins, Jacob O Kitzman, Siddhartha Jaiswal, Pinkal Desai, Charles Kooperberg, Alexander G Bick, Pradeep Natarajan, JoAnn E Manson, Eric A Whitsel, Alexander P Reiner, Michael C Honigberg.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging aging-related risk factor for cardiovascular disease (CVD). However, previous studies suggest that CHIP's relevance to CVD may diminish with advancing age.
OBJECTIVES: This study aimed to test the association of CHIP and its key subtypes with incident CVD in an older population.
METHODS: Participants in the Women's Health Initiative Long Life Study completed study assessments in 2012-2013 and underwent high-coverage sequencing (median depth 4,580×). The co-primary exposures were composite CHIP and TET2 CHIP. DNMT3A, ASXL1, JAK2, and non-DNMT3A CHIP were examined as secondary exposures. The primary outcome was incident coronary heart disease. Secondary outcomes were incident heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF), ischemic stroke, venous thromboembolism, and cardiovascular death. Multivariable-adjusted Cox models tested associations between CHIP and incident CVD.
RESULTS: Among 6,677 women (median age 80 years; median follow-up 10.1 years), 2,176 (32.6%) had any CHIP. TET2 CHIP was independently associated with incident coronary heart disease (aHR: 1.36 [95% CI: 1.05-1.77]; P = 0.02), whereas composite CHIP was not (aHR: 1.07 [95% CI: 0.89-1.28]; P = 0.49). Secondarily, TET2 CHIP was associated with HFpEF (aHR: 1.40 [95% CI: 1.03-1.90]; P = 0.03), ASXL1 CHIP with HFrEF (aHR: 3.16 [95% CI: 1.53-6.55]; P = 0.002), and JAK2 CHIP with ischemic stroke (aHR: 2.49 [95% CI: 1.17-5.30]; P = 0.02), venous thromboembolism (aHR: 2.71 [95% CI: 1.11-6.65]; P = 0.03), and cardiovascular death (aHR: 2.62 [95% CI: 1.68-4.11]; P < 0.001). No other significant associations were observed for composite or DNMT3A CHIP.
CONCLUSIONS: In an older female cohort, key CHIP subtypes (TET2, ASXL1, and JAK2) were associated with incident CVD, with associations that appeared to differ by CVD outcome. These findings suggest that CHIP remains associated with cardiovascular health into later life. (Women's Health Initiative [WHI]; NCT00000611).

Keywords: cardiovascular diseases; clonal hematopoiesis; coronary disease; heart failure; ischemic stroke; venous thromboembolism

DOI: https://doi.org/10.1016/j.jacc.2025.07.058

JACC CardioOncol. 2025 Aug;pii: S2666-0873(25)00255-8. [Epub ahead of print]7(5): 453-469

Cancer and Cardiovascular Disease: Shared Risk Factors, Mechanisms, and Clinical Implications: JACC: CardioOncology State-of-the-Art Review.

Laith Alhuneafat, Avirup Guha, Anne Blaes, Suma H Konety.

Cancer and cardiovascular disease (CVD) remain the leading causes of morbidity and mortality worldwide, with emerging evidence highlighting their complex and bidirectional interplay. Shared risk factors, including aging, systemic inflammation, metabolic dysregulation, and lifestyle behaviors, can contribute to their co-occurrence while underlying biological mechanisms such as oxidative stress, chronic inflammation, and clonal hematopoiesis further reinforce their connection. These mechanisms drive pathophysiological changes contributing to disease progression, increasing susceptibility to both conditions. This review explores the epidemiology, overlapping biological pathways, and risk factors linking cancer and CVD, emphasizing key mechanisms such as epigenetic modifications, immune system dysregulation, and cellular senescence. Future research should aim to identify biomarkers, refine risk models, and develop targeted strategies to mitigate disease burden and improve outcomes.

Keywords: bidirectional; cancer; cardiovascular disease; epigenetics; mechanisms; pathways; reverse cardio-oncology; risk factors

DOI: https://doi.org/10.1016/j.jaccao.2025.07.001

FASEB J. 2025 Aug 31. 39(16): e70964

Periodontal Ligament Stem Cell Aging in Age-Related Orthodontic Changes: Mechanisms and Rescue Strategies.

Jiayue Tang, Kai Yang.

With the growing demand for adult orthodontic treatment, age-related changes in clinical outcomes have emerged as significant challenges. However, effective strategies to improve outcomes in aging patients remain limited. Periodontal ligament stem cells (PDLSCs), a mechanosensitive subpopulation of mesenchymal stem cells, play a significant role in bone remodeling during orthodontic tooth movement (OTM) and are increasingly recognized as key contributors to the decline in orthodontic responsiveness with age. This review highlights the multifaceted role of PDLSCs in OTM, encompassing mechanosensation, mechanotransduction, and subsequent bone remodeling. It further examines how aging impairs PDLSC biology and potentially contributes to reduced orthodontic responsiveness in older individuals. Key aging-related mechanisms are described, including increased oxidative stress, disrupted mitochondrial homeostasis, impaired autophagy, loss of proteostasis, and epigenetic modifications. Dysregulation of intracellular signaling pathways further underscores the complexity of age-related functional decline. Based on these insights, emerging strategies for rescuing aged PDLSCs are summarized, offering a theoretical foundation for developing targeted interventions to enhance orthodontic outcomes in the aging population.

Keywords: age‐related changes; mitochondrial dysfunction; orthodontic; periodontal ligament stem cell; stem cell aging; stem cell rescue

DOI: https://doi.org/10.1096/fj.202501731R

Elife. 2025 Aug 27. pii: RP95880. [Epub ahead of print]13

Alteration of long- and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesis.

Katsuyuki Nishi, Taro Sakamaki, Akiomi Nagasaka, Kevin Shuolong Kao, Kay Sadaoka, Masahide Asano, Nobuyuki Yamamoto, Akifumi Takaori-Kondo, Masanori Miyanishi.

Myeloid-biased hematopoiesis is a well-known age-related alteration. Several possibilities, including myeloid-biased hematopoietic stem cell (HSC) clones, may explain this. However, the precise mechanisms remain controversial. Utilizing the Hoxb5 reporter system to prospectively isolate long-term HSCs (LT-HSCs) and short-term HSCs (ST-HSCs), we found that young and aged LT-HSCs co-transplanted into the same recipients demonstrated nearly equivalent myeloid lineage output, contrary to the theory of myeloid-biased HSC clones. Transcriptomics indicated no significant myeloid gene enrichment in aged LT-HSCs compared to their young counterparts. Instead, transplanting reconstituted young HSCs with the ratio of LT/ST-HSCs seen in aged mice can significantly skew the lineage output to myeloid cells. In addition, while the niche environment in the bone marrow minimally affects myeloid-biased hematopoiesis, aged thymi and spleens substantially hinder lymphoid hematopoiesis, resulting in further myeloid domination. Thus, we demonstrate that myeloid-biased hematopoiesis in aged mice originates due to alteration of the ratio between LT-HSCs and ST-HSCs rather than in heterogeneous HSC clones with various cell fates.

Keywords: aging; developmental biology; long-term hematopoietic stem cell; mouse; myeloid bias; regenerative medicine; self-renewal; short-term hematopoietic stem cell; stem cells

DOI: https://doi.org/10.7554/eLife.95880