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14 Publications visible to you, out of a total of 14
Cardiovascular risks and hazards associated with deep space exploration

Abstract (Expand)

Space flight exposes astronauts to a unique environment characterized by microgravity, ionizing radiation, and other stressors that can profoundly affect the human body. Deep-space exploration-type … missions to the Moon (NASA’s Artemis and Gateway programs), Mars, and beyond will introduce prolonged exposure to health hazards, including but not limited to isolation and confinement, sleep disruption, and exposure to different types and quantities of particle radiation (i.e., high-energy and atomic number – HZE). There are also logistical implications of traveling farther from low Earth orbit (LEO), including limited access to medical help and supplies. Currently, the known effects of space travel on the cardiovascular system include dysrhythmias, altered vascular compliance, dysautonomia, and induction of a pro-inflammatory state. It is not known how these concerns, and other potentially unknown cardiovascular risks, will manifest during and/or after exploration-type missions. This manuscript comprehensively reviews the cardiovascular disease risks associated with deep space exploration.

Authors: Agnieszka Brojakowska, Malik Bisserier, Abrisham Eskandari, Vineeta Jagana, Mary K. Khlgatian, Arsen Arakelyan, Jennifer Fogarty, Jason C. Kovacic, David A. Goukassian

Date Published: 23rd Jun 2026

Publication Type: Journal

Genomic Instability and Clonal Hematopoiesis in the Deep-Space Environment: The Role of Sex-Chromosome Asymmetry and High-LET Radiation

Abstract (Expand)

This paper examines how deep-space conditions in the Artemis program, including radiation, microgravity, and other stressors affect genomic stability in blood-forming cells, with a focus on clonal … hematopoiesis and sex-specific differences in DNA repair and mutation risk. Studies show space conditions promote mutations in hematopoietic stem cells, with sex-specific effects: males are more vulnerable to Y chromosome loss and structural damage, while females may experience increased epigenetic instability despite protective redundancy from the X chromosome; these risks are amplified by combined stressors like radiation, oxidative stress, and circadian disruption. Sex chromosome differences play a key role in radiation-induced mutations and clonal expansion, highlighting the need for personalized, sex-specific medical monitoring and countermeasures rather than a uniform approach for astronauts on long-duration missions.

Authors: Roksana Zakharyan, Ani Stepanyan, Arpine Minasyan, Suren Davitavyan, Gisane Lazaryan, Siras Hakobyan, Agnieszka Brojakowska, Malik Bisserier, Susmita Sahoo, Shihong Zhang, Venkata Naga Srikanth Garikipati, Mary K. Khlgatian, Arsen Arakelyan, David A. Goukassian

Date Published: 23rd Apr 2026

Publication Type: Journal

Persistence of Western Diet-Associated Pathway Activity Profiles in Ventricular Tissues

Abstract (Expand)

The consumption of a Western diet (WD), characterized by high levels of fats and sugars, is strongly associated with adverse cardiovascular outcomes. In this case-control study, we evaluated long-term … alterations in signaling pathway activities in the left (LV) and right (RV) ventricular tissues of C57Bl/6J mice that were exposed to WD starting at 300 days of age for 125 days before switching to a normal diet (ND). LV and RV tissues were collected at 530 days and subjected to RNA sequencing. Pathway activity for 40 signaling pathways (comprising 709 pathway branches/sinks) was calculated using the topology-aware Pathway Signal Flow (PSF) algorithm, which assesses signal propagation along a pathway based on gene expression levels of its components and their interactions. We observed significant perturbations in 14 pathway branches specifically in LV tissue of male mice, 105 days after the ND switch. These alterations included the downregulation of cardioprotective VEGF signaling and the upregulation of pro-fibrotic TGF-beta signaling, suggesting lasting cardiovascular risks. Furthermore, strong signaling was detected in the cGMP-PKG and FOXO pathways linked to cardiac failure. Finally, pro- and anti-apoptotic signals were simultaneously upregulated, accompanied by the downregulation of cell cycle inhibitors. Notably, no significant gene expression changes were detected in the left ventricular tissue of females, and no significant differences were observed in right ventricular tissue in either sex. These findings suggest that the effects of a Western diet may persist even after transitioning to a healthier diet. Further studies are needed to elucidate the diet-associated risks and develop strategies to mitigate these long-term effects.

Authors: Tamara Sirunyan, Gisane Lazaryan, Siras Hakobyan, Suren Davitavyan, Ani Stepanyan, Agnieszka Brojakowska, Mary Khlgatian, Malik Bisserier, Shihong Zhang, David Goukassian, Arsen Arakelyan

Date Published: 2nd Jan 2026

Publication Type: Journal

Long-Term Impact of Western Diet on Right Ventricular Transcriptome: Uncovering Sex-Specific Patterns in C57BL/6J Mice

Abstract (Expand)

The Western diet (WD) has been linked to various structural and functional alterations in the left ventricle (LV), but the molecular response of the right ventricle (RV) remains largely unknown. Given … the RV’s distinct anatomical and functional characteristics, it is crucial to understand how long-term WD exposure affects RV gene expression, especially in a sex-specific context. Our objective was to perform gene expression profiling of the RV late responses to WD in wild-type mice. Male and female C57BL/6J mice were fed a WD for 125 days from 300 to 425 days of age, and RV tissues were collected at 530 and 640/750 (female/male) days. mRNA sequencing was performed on RV tissues to identify differentially expressed genes (DEGs) between WD-fed and normal diet (ND)-fed groups. Data processing and analysis were conducted using the STAR aligner and DESeq2. WD-induced RV transcriptomic changes were characterized by differential expression of genes associated with cardiac remodeling and transcriptional regulation in both sexes. In females, additional genes showing altered expression were associated with immune response, whereas in males, changes were more limited, primarily involving genes related to circadian rhythm and cardiac remodeling. Echocardiography revealed modest, sex-specific differences: WD-fed females showed a decrease in right-ventricular internal diameter in diastole and a trend toward increased pulmonary trunk diameter, whereas males showed no notable changes. These exploratory results suggest that WD is associated with modest transcriptomic changes in the RV in both sexes, with only minor structural differences observed in females, indicating subtle sex-specific effects after a switch to normal chow.

Authors: Ani Stepanyan, Siras Hakobyan, Agnieszka Brojakowska, Malik Bisserier, Roksana Zakharyan, Suren Davitavyan, Tamara Sirunyan, Gisane Khachatryan, Mary K. Khlgatian, Shihong Zhang, Ania Baghoomian, Susmita Sahoo, Lahouaria Hadri, Venkata Naga Srikanth Garikipati, Arsen Arakelyan, David A. Goukassian

Date Published: 26th Dec 2025

Publication Type: Journal

Long-term Pathway Activation in Cardiac Ventricular Tissues after Gamma and simGCRsim Irradiation.

Abstract (Expand)

Space radiation represents a significant health risk for deep-space exploration, yet its long-term effects on cardiovascular function remain poorly understood. While our previous studies have highlighted … persistent transcriptional changes in left ventricular (LV) and right ventricular (RV) tissues after a single whole-body irradiation in mice, a systems-level understanding of pathway activity deregulation is lacking. To address this gap, we applied the Pathway Signal Flow (PSF) algorithm to analyze long-term pathway activity alterations in LV and RV tissues of C57Bl/6J mice exposed to gamma radiation (100 cGy 137Cs) or the simplified Galactic Cosmic Ray simulation (simGCRsim, 50 cGy 500 MeV/n) composition of ion beams. RNA sequencing data were analyzed to assess pathway activity changes, sex-specific effects, and ventricular differences 440 days post-irradiation. We observed marked sex- and ventricle-specific differences in pathway deregulation. Left ventricular tissues in females exhibited broad signaling pathway alterations after simGCRsim exposure, particularly in immune response, cytoskeletal remodeling, and survival-related pathways (e.g., NF-κB, VEGF, and MAPK). In contrast, male RV tissues demonstrated higher pathway deregulation than LV, particularly in PPAR, NF-κB, and HIF-1 pathways, implicating metabolic disruption and survival adaptations. Furthermore, simGCRsim exposure induced greater long-term pathway perturbations than gamma rays. Our findings suggest that sex-dependent and ventricle-specific signaling alterations contribute to long-term cardiovascular risks following space irradiation. Notably, VEGF and NF-κB signaling emerge as key regulators of cardiac adaptation in females. Future studies in larger cohorts, incorporating early-stage molecular responses and broader pathway analyses, are needed to refine cardiovascular risk assessments for space travel.

Authors: Gisane Khachatryan, Tamara Sirunyan, Siras Hakobyan, Suren Davitavyan, Roksana Zakharyan, Ani Stepanyan, Agnieszka Brojakowska, Mary K Khlgatian, Malik Bisserier, Shihong Zhang, David A Goukassian, Arsen Arakelyan

Date Published: 25th Sep 2025

Publication Type: Journal

The effects of space radiation on the transcriptome of heart right ventricle tissue

Abstract (Expand)

Deep space represents a challenging environment for human exploration and can be accompanied by harmful health-related risks. We aimed to assess the effect of simplified galactic cosmic ray simulated … (simGCRsim) and gamma (γ) ionizing radiation (IR) on transcriptome changes in right ventricular (RV) tissue after a single low dose (0.5 Gy, 500 MeV/nucleon) full body exposure in C57BL/6J male and female mice. In females, no differentially expressed genes (DEGs) and only 2 upregulated genes in males exposed to γ-IR were revealed. In contrast, exposure to simGCRsim-IR resulted in 4 DEGs in females and 371 DEGs in males, suggesting longer-lasting and sex-biased DEGs after simGCRsim-IR. Overrepresentation analysis of DEGs in simGCRsim-IR males revealed significant enrichment in pathways related to muscle contraction, hypertrophic cardiomyopathy, oxytocin release, the regulation of cytoskeleton, and genes associated with Alzheimer’s, Huntington’s, and Parkinson’s diseases. Our results suggested the RV transcriptome exhibits distinct responses after exposure based on both the IR and sex.

Authors: Roksana Zakharyan, Siras Hakobyan, Agnieszka Brojakowska, Malik Bisserier, Shihong Zhang, Mary K. Khlgatian, Amit Kumar Rai, Suren Davitavyan, Ani Stepanyan, Tamara Sirunyan, Gisane Khachatryan, Susmita Sahoo, Venkata Naga Srikanth Garikipati, Arsen Arakelyan, David A. Goukassian

Date Published: 21st Jul 2025

Publication Type: Journal

Long-lasting sex-specific alteration in left ventricular cardiac transcriptome following gamma and simGCRsim radiation

Abstract (Expand)

Space irradiation (IR) is an important health risk for deep-space missions. We reported heart failure with preserved ejection fraction like cardiac phenotype 660-days following exposure to a single-dose … of a simplified galactic cosmic ray simulation (simGCRsim) only in males with functional and structural impairment in left ventricular (LV) function. This sex-based dichotomy prompted us to investigate sex-specific changes in the LV transcriptome in three-month-old male and female mice exposed to 137Cs-γ- or simGCRsim-IR. Non-IR male and female (10 each) mice served as controls. LVs were collected at 440/660- and 440/550-days post-IR, male and female, respectively. RNA sequencing, differential gene expression, and functional annotation were performed on tissues from 5 mice/group. Sex and post-IR time points had the greatest influence on gene expression, surpassing the IR-type effects. SimGCRsim-IR showed more persistent transcriptome changes than γ-IR. We suggest that the single IR effects can persist up to 550-660 days, with overwhelmingly sex-biased responses at individual gene expression level.

Authors: Roksana Zakharyan, Siras Hakobyan, Agnieszka Brojakowska, Suren Davitavyan, Ani Stepanyan, Tamara Sirunyan, Gisane Khachatryan, Mary K. Khlgatian, Malik Bisserier, Shihong Zhang, Susmita Sahoo, Lahouaria Hadri, Venkata Naga Srikanth Garikipati, Arsen Arakelyan, David A. Goukassian

Date Published: 18th Feb 2025

Publication Type: Journal

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