Background Reperfusion accounts for a substantial fraction of the myocardial injury occurring with ischemic heart disease. Yet, no standard therapies are available targeting reperfusion injury. Here, we tested the hypothesis that SAHA, a histone deacetylase (HDAC) inhibitor FDA-approved for cancer treatment, will blunt reperfusion injury. Methods and Results Twenty-one rabbits were randomized into 3 groups: a) vehicle control, b) SAHA pretreatment (one day prior and at surgery), and c) SAHA treatment at the time of reperfusion only. Each arm was subjected to ischemia/reperfusion surgery (I/R, 30min coronary ligation, 24h reperfusion). Additionally cultured neonatal and adult rat ventricular cardiomyocytes were subjected to simulated I/R (sI/R) to probe mechanism. SAHA reduced infarct (those reduction inhibitor, SAHA, infarct size in a large animal model, even when delivered in the clinically relevant context of reperfusion. The cardioprotective effects of SAHA during I/R occur, at least in part, through induction of autophagic flux. assayed in both rabbit myocardium and in mice harboring an RFP-GFP-LC3 transgene. In cultured myocytes subjected to sI/R, SAHA pretreatment reduced cell death by 40%. This eduction in cell death correlated with increased autophagic activity in SAHA-treated cells. RNAi-mediated knockdown of ATG7 and ATG5, essential autophagy proteins, abolished SAHA's cardioprotective effects. Conclusions The FDS-approved anti-cancer HDAC inhibitor, SAHA, reduces myocardial infarct size in a large animal model, even when delivered in the clinically relevant context of reperfusion. The cardioprotective effects of SAHA during I/R occur, at least in part, through induction of autophagic flux.

Although advances in care have spurred improvements in cardiovascular outcomes, cardiovascular disease remains the leading cause of death in the United States and around the world. Previous declines in cardiovascular disease mortality have slowed and even reversed for certain demographics. Further concerns exist with regard to cardiovascular drug innovation, quality of care, and healthcare costs. The Value in Healthcare Initiative–Transforming Cardiovascular Care, a collaboration of the American Heart Association and Duke University, Robert J. Margolis, MD, Center for Health Policy, aims to increase access to and affordability of cardiovascular treatment and to decrease barriers to care. The following Call to Action describes trends in cardiovascular care, identifies gaps in areas of cardiovascular disease prevention and treatment, highlights challenges with medical product innovation, and finally, outlines a series of learning collaboratives that will aid in the development of road maps for transforming cardiovascular care.

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Light-assisted 3D direct-printing of biomaterials and cellular-scaffolds has the potential to develop novel lab-on-a-chip devices (LOCs) for a variety of biomedical applications, from drug discovery and diagnostic testing to in vitro tissue engineering and regeneration. Direct-writing describes a broad family of fabrication methods that typically employ computer-controlled translational stages to manufacture structures at multi-length scales. This review focuses on light-assisted direct-write fabrication for generating 3D functional scaffolds with precise micro- and nano-architecture, using both synthetic as well as naturally derived biomaterials. Two bioprinting approaches are discussed in detail - projection printing and laser-based systems - where each method is capable of modulating multiple scaffold parameters, such as 3D architecture, mechanical properties (e.g. stiffness), Poisson's ratio, chemical gradients, biological cell distributions, and porosity. The light-assisted direct-writing techniques described in this review provide the reader with alternative approaches to fabricate 3D biomaterials for utility in LOCs.

Addressing the pervasive gaps in knowledge and care delivery to reduce sex-based disparities and achieve equity is fundamental to the American Heart Association’s commitment to advancing cardiovascular health for all by 2024. This presidential advisory serves as a call to action for the American Heart Association and other stakeholders around the globe to identify and remove barriers to health care access and quality for women. A concise and current summary of existing data across the areas of risk and prevention, access and delivery of equitable care, and awareness and education provides a framework to consider knowledge gaps and research needs critical toward achieving significant progress for the health and well-being of all women.

Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA’s new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force’s main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.

Structures that exhibit fractal geometries are typically self-similar and iterative. Fractal patterns appear in nature as approximations of mathematical abstractions, yet exist as artifacts of specific processes having reached optimized conditions in the presence of various forces and movements. In this paper, we focus on 3D printing of fractal geometry using computer designed and user adjusted patterns. Various biocompatible hydrogel structures were printed from a photopolymerizable poly­(ethylene glycol) diacrylate via maskless stereolithography. This digital micromirror device-based projection printing platform is capable of imbuing fractal topographic patterns into a more cell accommodating medium. Several fractal structures were printed mimicking the energy and material pattern optimization achieved by fractal geometries found in nature. The resulting structures were confirmed with bright-field and SEM microscopy. Complex geometries were obtained at many angles, and various heights that exhibited self-similar geometries. The surfaces of the hydrogel structures were conjugated with fibronectin cell adhesion protein and then seeded with cells. Fluorescent staining of actin and nuclei for both murine myoblast cells and human mesenchymal stem cells were conducted to determine the feasibility of these designed cell adhesive topographies to influence aggregate cells. This flexible and versatile platform can be extended to fabricate other complex biomimetic designs for biological applications, such as tissue engineering.