Coronary artery disease (CAD) is the leading form of cardiovascular disease (CVD), which is the primary cause of mortality worldwide. It is a complex disease with genetic and environmental risk factor contributions. Reports in human and mammalian models elucidate age-associated changes in cardiac function. The diverse mechanisms involved in cardiac diseases remain at the center of the research interest to identify novel strategies for prevention and therapy. Zebrafish (Danio rerio) have emerged as a valuable vertebrate model to study cardiovascular development over the last few decades. The facile genetic manipulation via forward and reverse genetic approaches combined with noninvasive, high-resolution imaging and phenotype-based screening has provided new insights to molecular pathways that orchestrate cardiac development. Zebrafish can recapitulate human cardiac pathophysiology due to gene and regulatory pathways conservation, similar heart rate and cardiac morphology and function. Thus, generations of zebrafish models utilize the functional analysis of genes involved in CAD, which are derived from large-scale human population analysis. Here, we highlight recent studies conducted on cardiovascular research focusing on the benefits of the combination of genome-wide association studies (GWAS) with functional genomic analysis in zebrafish. We further summarize the knowledge obtained from zebrafish studies that have demonstrated the architecture of the fundamental mechanisms underlying heart development, homeostasis and regeneration at the cellular and molecular levels.

Cardiovascular diseases (CVDs) are the prevalent cause of mortality worldwide. A combination of environmental and genetic effectors modulates the risk of developing them. Thus, it is vital to identify candidate genes and elucidate their role in the manifestation of the disease. Large-scale human studies have revealed the implication of Craniofacial Development Protein 1 (CFDP1) in Coronary Artery Disease (CAD). CFDP1 belongs to the evolutionary conserved Bucentaur (BCNT) family, and to date, its function and mechanism of action in Cardiovascular Development are still unclear. We utilized zebrafish to investigate the role of cfdp1 in the developing heart due to the high genomic homology, similarity in heart physiology, and ease of experimental manipulations. We showed that cfdp1 was expressed during development, and we tested two morpholinos and generated a cfdp1 mutant line. The cfdp1^−/− embryos developed arrhythmic hearts and exhibited defective cardiac performance, which led to a lethal phenotype. Findings from both knockdown and knockout experiments showed that abrogation of cfdp1 leads to downregulation of Wnt signaling in embryonic hearts during valve development but without affecting Notch activation in this process. The cfdp1 zebrafish mutant line provides a valuable tool for unveiling the novel mechanism of regulating cardiac physiology and function. cfdp1 is essential for cardiac development, a previously unreported phenotype most likely due to early lethality in mice. The detected phenotype of bradycardia and arrhythmias is an observation with potential clinical relevance for humans carrying heterozygous CFDP1 mutations and their risk of developing CAD.

Background: Hypertension poses a significant global health burden and is associated with cardiovascular morbidity. Chios mastic gum (CMG), derived from Pistacia lentiscus var. Chia, shows potential as a phytotherapeutic agent, due to its multifaceted beneficial effects. However, its anti-hypertensive effects and vascular, circulatory, and renal-related dysfunction, have not been thoroughly investigated. Herein, we aimed to explore the antihypertensive potential of CMG, focusing on vascular and renal endothelium, in vivo. Methods: Two models of hypertension in male rats, induced by Angiotensin II and Deoxycorticosterone acetate (DOCA)–high-salt administration, were utilized. CMG was administered at 220 mg/kg daily for four weeks after hypertension onset and blood pressure was measured non-invasively. Whole blood RNA sequencing, metabolomics, real-time PCR, and Western blot analyses of kidney and aorta tissues were additionally performed. Results: CMG significantly lowered systolic, diastolic, and mean blood pressure in both models. RNA sequencing revealed that CMG modulated immunity in the Angiotensin II model and metabolism in the DOCA–HS model. CMG downregulated genes related to oxidative stress and endothelial dysfunction and upregulated endothelial markers such as Vegfa. Metabolomic analysis indicated improved endothelial homeostasis via lysophosphatidylinositol upregulation. Conclusions: CMG emerges as a potent natural antihypertensive therapy, demonstrating beneficial effects on blood pressure and renal endothelial function.

Hypertension is a chronic, multifactorial disease, leading to high cardiovascular morbidity and mortality globally. Despite the advantages of pharmaceutical treatments, natural products have gained scientific interest due to their emerging phytotherapeutic properties. Chios mastic is a natural Greek product, consisting of bioactive compounds which modify microRNAs’ (small, expression-regulating molecules) expression. In this study, we investigated the antihypertensive properties of Chios mastic through the assessment of miR-21 levels. Herein, plasma samples of 57 individuals with hypertension, recruited for the purposes of the HYPER-MASTIC study, were analyzed. This was a clinical trial with Chios mastic supplements in which the patients were divided into groups receiving high and low mastic doses and placebo supplements, respectively. miR-21 was significantly upregulated in patients compared to normotensive individuals. Mean changes in miR-21 levels were statistically significant, after adjusting for sex and age, between the placebo and low-dose group and between the low- and high-dose group. Post-intervention miR-21 levels were positively associated with night-time systolic blood pressure, pulse pressure, and central systolic mean arterial pressure and negatively associated with night-time pulse wave velocity in the low-dose group. Our findings suggest a potential implication of miR-21 in the association of Chios mastic with night-time blood pressure measurements.