Cardiology · Medical Literature
The Vascular Genome as a Therapeutic Target: A Systematic Review of CRISPR-based Gene Editing In Vascular Disease.
Abstract
Despite advances in therapy, arterial, venous, and pulmonary vascular diseases remain leading causes of morbidity and mortality. Persistent endothelial dysfunction, inflammation, oxidative stress, and maladaptive vascular remodeling continue to drive disease progression and residual risk. CRISPR/Cas9 technology offers a unique opportunity to modify the molecular pathways underlying vascular pathophysiology directly. The PRISMA 2020 guidelines guided the systematic review. The databases PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and Google Scholar were searched from their inception until September 2025 for experimental and/or clinical studies evaluating the application of CRISPR/Cas9 on vascular disease. Included were in vitro studies, animal model studies, and early-phase human studies aimed at targeting the endothelial cell regulatory pathways, inflammatory pathways, metabolic remodeling processes, and hereditary causes of vasculopathy. Seventeen studies met the inclusion criteria. CRISPR technologies targeting PCSK9, NOS3, HIF1A, NLRP3, METTL4, BMPR2, and ACTA2 were identified to enhance repair mechanisms in endothelial cells, regulate inflammation, modulate lipid metabolism, and remodel the vascular system. The human studies demonstrated sustained gene silencing effects following a single dose of CRISPR-induced in vivo editing. The use of CRISPR technology to edit cell genomes offers potential to alter disease progression in vascular medicine, with a growing body of translational evidence supporting the feasibility and durability of the approach.
Clinical relevance
Can CRISPR/Cas9-based gene editing targeting vascular molecular pathways (including PCSK9, NOS3, HIF1A, NLRP3, METTL4, BMPR2, and ACTA2) effectively modify the pathophysiology of arterial, venous, and pulmonary vascular diseases in experimental and/or clinical studies? __SNAPSHOT__ {"studyDesign":"Systematic review (PRISMA 2020-compliant) of experimental and early-phase human studies","setting":"Multi-database search: PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and Google Scholar; inception through September 2025","sampleSize":"17 studies met inclusion criteria; individual study sample sizes not reported in the available abstract","population":"In vitro cell models, animal models, and early-phase human study participants investigated for arterial, venous, and pulmonary vascular diseases; specific inclusion criteria include studies targeting endothelial cell regulatory pathways, inflammatory pathways, metabolic remodeling, and hereditary vasculopathies","intervention":"CRISPR/Cas9-based gene editing targeting seven vascular genomic loci: PCSK9 (lipid metabolism/endothelial dysfunction), NOS3 (nitric oxide signaling), HIF1A (hypoxia-inducible metabolic reprogramming), NLRP3 (inflammasome-mediated vascular inflammation), METTL4 (RNA methylation/epigenetic remodeling), BMPR2 (pulmonary arterial hypertension), and ACTA2 (smooth muscle cell function/hereditary vasculopathy)","comparator":"Varies by included study (wild-type controls, untreated disease models, or standard-of-care comparators); not uniformly reported across the systematic review","primaryOutcome":"Efficacy and applicability of CRISPR/Cas9 in enhancing endothelial repair, regulating vascular inflammation, modulating metabolic remodeling, and correcting hereditary causes of vasculopathy; specific quantitative primary endpoints not reported in the available abstract","followUp":"Not reported in the available abstract; varies by individual included study","fundingSource":"Not reported in the available abstract"}
Key findings
Based on the truncated abstract provided (PMID 42570142, Cardiovascular Toxicology, 2026), 17 studies met PRISMA 2020 inclusion criteria. Seven CRISPR gene targets were identified across the vascular disease spectrum: PCSK9 (atherosclerosis and endothelial lipid metabolism), NOS3 (endothelial nitric oxide bioavailability), HIF1A (hypoxic and metabolic vascular reprogramming), NLRP3 (inflammasome-driven vascular inflammation), METTL4 (epitranscriptomic regulation of vascular remodeling), BMPR2 (pulmonary arterial hypertension pathobiology), and ACTA2 (hereditary smooth muscle cell vasculopathy). The abstract states these technologies were 'identified to enhance repair mechanisms in endothelial cells, regulate inflammat—' (text truncated). No quantitative effect sizes, confidence intervals, p-values, NNT, or NNH values are reported in the available abstract. No adverse event rates or safety outcomes are quantitatively reported. All findings described here are derived solely from the abstract as provided; the full-text analysis may contain additional quantitative data not accessible for this summary.
Practice implications
This systematic review catalogues the emerging landscape of CRISPR/Cas9 gene editing applied to vascular disease biology, spanning atherosclerosis, pulmonary arterial hypertension, and hereditary vasculopathies. The identification of seven therapeutically relevant genomic targets across distinct vascular pathophysiological axes (lipid metabolism, nitric oxide signaling, hypoxia response, innate immune activation, RNA methylation, BMP signaling, and smooth muscle contractility) demonstrates the breadth of the vascular genome as a tractable therapeutic target. However, because this review encompasses in vitro studies, animal models, and early-phase human studies without reported pooled quantitative outcomes, no conclusions about clinical efficacy, optimal dosing, or patient-level benefit can be drawn. The findings cannot yet be generalized to defined patient populations, as the individual studies almost certainly represent heterogeneous disease states, model systems, and editing modalities. Patients who are most likely underrepresented include those with advanced multivessel disease, elderly patients, patients with significant comorbidities, and those from low- and middle-income countries. The body of evidence is preclinical-predominant, and this summary is further limited to the abstract alone; the full text may contain additional outcomes, meta-analytic data, or subgroup analyses not captured here. CRITICAL NOTE: Only the abstract was available for this summary; findings should be interpreted with appropriate caution pending full-text review. __LIMITATIONS__ 1. Only 17 studies met inclusion criteria, limiting pooled statistical power and generalizability. 2. The review spans heterogeneous study types (in vitro, animal, and early-phase human), making cross-study synthesis and clinical extrapolation methodologically hazardous. 3. No quantitative pooled effect sizes, confidence intervals, or p-values are reported in the available abstract, precluding assessment of magnitude or statistical precision of claimed benefits. 4. CRISPR off-target genotoxicity, chromosomal structural variations, and Cas9 immunogenicity—recognized challenges in therapeutic gene editing—are not quantitatively addressed in the abstract. 5. Endothelial cells are inherently resistant to viral vector transduction, complicating in vivo delivery; delivery system performance across included studies is not uniformly characterized. 6. Animal-to-human translational validity is unestablished for most targets reviewed; early-phase human study results are not separately quantified. 7. The abstract is truncated, meaning key conclusions, safety data, and the completeness of the review's findings cannot be fully assessed. 8. Funding source is not reported, precluding conflict-of-interest assessment. 9. Publication bias cannot be excluded given the small number of included studies. 10. Long-term durability of gene edits and permanence of therapeutic effect are not addressed in the available abstract. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ This PRISMA 2020-compliant systematic review identifies seven CRISPR/Cas9 gene targets (PCSK9, NOS3, HIF1A, NLRP3, METTL4, BMPR2, ACTA2) with mechanistic plausibility for vascular disease modification across arterial, venous, and pulmonary beds, based on 17 heterogeneous experimental and early-phase human studies. No pooled quantitative clinical outcomes, safety data, or effect sizes are reported in the available abstract, and the evidence base remains predominantly preclinical. This body of work does not yet support changes in clinical practice, but meaningfully maps the vascular genome targets most likely to inform next-generation gene editing trials pending full-text review and independent replication.