Angiogenesis precedes cardiomyocyte migration in regenerating mammalian hearts

Ingason, Arnar B.; Goldstone, Andrew B.; Paulsen, Michael J.; Thakore, Akshara D.; Truong, Vi N.; Edwards, Bryan B.; Eskandari, Anahita; Bollig, Tanner; Steele, Amanda N.; Woo, Y. Joseph

doi:10.1016/j.jtcvs.2017.08.127

Cited by 61 publications

(60 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To perform LAD ligation in neonatal rats, we applied our experience with topical cooling and hypothermic circulatory arrest in neonatal mice [26,39] to an upscaled rat model. We observed that P1 rats required 7 min of cooling on ice to induce apnea and asystole that reproducibly lasted the duration of surgery.…”

Section: Discussionmentioning

confidence: 99%

“…This process results in gradual myocardial regeneration and complete LV functional recovery by 3 weeks post-MI. Future studies aimed at elucidating the mechanisms involved with natural heart regeneration are necessary, including the role of angiogenesis [26,39,41], the immune system [42,43], the endocrine system [44], and the nervous system [45].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model

Wang

Paulsen

Hironaka

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

Newborn mice and piglets exhibit natural heart regeneration after myocardial infarction (MI). Discovering other mammals with this ability would provide evidence that neonatal cardiac regeneration after MI may be a conserved phenotype, which if activated in adults could open new options for treating ischemic cardiomyopathy in humans. Here, we hypothesized that newborn rats undergo natural heart regeneration after MI. Using a neonatal rat MI model, we performed left anterior descending coronary artery ligation or sham surgery in one-day-old rats under hypothermic circulatory arrest (n = 74). Operative survival was 97.3%. At 1 day post-surgery, rats in the MI group exhibited significantly reduced ejection fraction (EF) compared to shams (87.1% vs. 53.0%, p < 0.0001). At 3 weeks post-surgery, rats in the sham and MI groups demonstrated no difference in EF (71.1% vs. 69.2%, respectively, p = 0.2511), left ventricular wall thickness (p = 0.9458), or chamber diameter (p = 0.7801). Masson’s trichome and picrosirius red staining revealed minimal collagen scar after MI. Increased numbers of cardiomyocytes positive for 5-ethynyl-2′-deoxyuridine (p = 0.0072), Ki-67 (p = 0.0340), and aurora B kinase (p = 0.0430) were observed within the peri-infarct region after MI, indicating ischemia-induced cardiomyocyte proliferation. Overall, we present a neonatal rat MI model and demonstrate that newborn rats are capable of endogenous neocardiomyogenesis after MI.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model

Wang

Paulsen

Hironaka

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…5a). Revascularization of the regenerating ventricle has been shown to be essential for correct tissue restoration in both zebrafish 49,50 and murine models 51 , while several studies have shown that autophagy regulation is necessary for the proper adaptive response of the vascular system 12 .…”

Section: Scientific Reports |mentioning

confidence: 99%

Autophagy Activation in Zebrafish Heart Regeneration

Chávez

Morales

López-Crisosto

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Autophagy is an evolutionarily conserved process that plays a key role in the maintenance of overall cellular health. While it has been suggested that autophagy may elicit cardioprotective and pro-survival modulating functions, excessive activation of autophagy can also be detrimental. In this regard, the zebrafish is considered a hallmark model for vertebrate regeneration, since contrary to adult mammals, it is able to faithfully regenerate cardiac tissue. Interestingly, the role that autophagy may play in zebrafish heart regeneration has not been studied yet. In the present work, we hypothesize that, in the context of a well-established injury model of ventricular apex resection, autophagy plays a critical role during cardiac regeneration and its regulation can directly affect the zebrafish regenerative potential. We studied the autophagy events occurring upon injury using electron microscopy, in vivo tracking of autophagy markers, and protein analysis. Additionally, using pharmacological tools, we investigated how rapamycin, an inducer of autophagy, affects regeneration relevant processes. Our results show that a tightly regulated autophagic response is triggered upon injury and during the early stages of the regeneration process. Furthermore, treatment with rapamycin caused an impairment in the cardiac regeneration outcome. These findings are reminiscent of the pathophysiological description of an injured human heart and hence put forward the zebrafish as a model to study the poorly understood double-sword effect that autophagy has in cardiac homeostasis.Autophagy is an evolutionarily conserved self-degradation process that involves the engulfment, degradation and recycling of dysfunctional or damaged cellular components 1 . It assumes key roles during adaptation to nutrient starvation 1,2 elimination of pathogens 3 , while it is fundamental in cell differentiation and tissue patterning during development 4 and regeneration 5-7 . In the heart, autophagy has been found to be essential for cardiac development, morphogenesis and cardiomyocyte differentiation 8-10 , and is recognized as a highly relevant housekeeping mechanism for the maintenance of the post-mitotic, essentially unreplaceable, cardiomyocytes that constitute it 11 . On the other hand, autophagy has been found to be involved in the onset and progression of many cardiovascular diseases, such as myocardial infarction and chronic heart failure, where it is a riddle how autophagy may have a protective role, while at the same time, aggravating cardiac dysfunction 12,13 . Because of this, autophagy has been recognized as a potential therapeutic target for cardiovascular diseases, though finding the right strategy to use autophagy activation to improve clinical outcome has not been possible until now 14,15 .The zebrafish (Danio rerio) has become a popular vertebrate model organism because of its superb regenerative capacities. Experimental models of heart amputation 16 , cardiomyocyte-specific genetic ablation 17 , hypoxic damage and ischemia/reperfusion ...

show abstract

“…14 They concluded that pre-establishing the vasculature is paramount to supporting cardiomyocyte ingrowth and survival, similar to the prior obervations of Porrello et al 15,16 These findings are reminiscent of the therapeutic principles noted with angiogenic pre-treatment of myocardial scar.…”

mentioning

confidence: 61%