The human heart beats over 100,000 times per day, but when this intricate system fails, the consequences are devastating. In 2018, leading scientists gathered to plot a revolutionary course against cardiovascular disease.
Every 36 seconds, one person in the United States dies from cardiovascular disease. This startling statistic fuels an urgent global race to decode the heart's deepest secrets—a race accelerated each year when brilliant minds converge at the Basic Cardiovascular Sciences (BCVS) Scientific Sessions. The 2018 gathering in San Antonio, Texas, served as a crucial battleground in this fight, showcasing groundbreaking innovations poised to transform how we understand, diagnose, and treat heart disease.
Induced pluripotent stem cells can be reprogrammed into beating heart cells, enabling personalized cardiovascular medicine and disease modeling.
The theme "Innovations in Cardiovascular Research" dominated the conference, where researchers presented revolutionary findings spanning molecular biology, tissue engineering, and computational medicine. From the promising realm of induced pluripotent stem cells that can be reprogrammed into beating heart cells to advanced biomaterials that can integrate with living tissue, the sessions painted a future where repairing damaged hearts might become as routine as mending a broken bone. This article delves into the most exciting discoveries from BCVS 2018, making complex science accessible and revealing how these advances are forging a path toward conquering heart failure.
To appreciate the breakthroughs presented at BCVS 2018, we must first understand a fundamental process in heart disease: cardiac remodeling. Imagine your heart as a well-designed pump. When injured—by a heart attack, high blood pressure, or other stressors—it undergoes structural changes in a desperate attempt to maintain function. This phenomenon, known as cardiac remodeling, encompasses molecular, cellular, and interstitial changes that manifest as alterations in the heart's size, mass, geometry, and function 1 .
Initially, these changes might be compensatory, helping the stressed heart maintain output. However, when sustained, they become maladaptive, leading to a progressive decline in cardiac function. The clinical implications are severe: cardiac remodeling often results in poor prognosis due to its association with ventricular dysfunction and malignant arrhythmias 1 . Approximately 50% of patients diagnosed with cardiac dysfunction will die within five years, with about 40% dying within one year after hospitalization for cardiac failure 1 .
Mortality within 5 years of cardiac dysfunction diagnosis
Understanding these mechanisms provides the essential context for the revolutionary research unveiled at BCVS 2018, where scientists presented new strategies to interrupt this destructive cascade.
One of the most compelling presentations at BCVS 2018 detailed a crucial experiment that illuminated a key molecular mechanism driving the transition from compensatory hypertrophy to frank heart failure. Cardiac hypertrophy—the thickening of heart muscle—begins as an adaptive response to stress but frequently evolves into a maladaptive state characterized by dysfunctional pumping and dangerous electrical abnormalities.
The experimental results revealed fascinating insights with significant clinical implications:
STIM1 silencing prevented hypertrophy in response to pressure overload, but unexpectedly accelerated the progression to heart failure .
The timing of STIM1 manipulation proved critical—while early inhibition prevented hypertrophy, later inhibition in already hypertrophied hearts reversed the thickening but compromised function .
Mechanistically, STIM1 was found to associate with ORAI1/3 channels to mediate calcium influx that activates mTORC2, which in turn phosphorylates Akt . Activated Akt suppresses GSK-3β, a known brake on hypertrophic growth, thereby permitting the compensatory hypertrophy necessary for maintaining cardiac output under stress .
This experiment demonstrated the double-edged nature of cardiac hypertrophy: while ultimately detrimental if sustained, it serves as a crucial temporary adaptation to hemodynamic stress.
The findings suggest that therapeutic interventions must be carefully timed, as completely suppressing the hypertrophic response might do more harm than good.
Cardiovascular research breakthroughs depend on sophisticated experimental tools. The BCVS 2018 sessions highlighted several cutting-edge reagents and models that are driving the field forward.
| Model Type | Examples | Advantages | Limitations |
|---|---|---|---|
| In Vitro | Neonatal rat cardiomyocytes, immortalized cell lines | Controlled environment, high-throughput capability, reduced animal use | Lack physiological complexity, immature cell characteristics 6 |
| Small Animal | Mouse transverse aortic constriction, rat myocardial infarction | Genetic manipulability, lower cost, established protocols | Physiological differences from humans, smaller size for procedures 6 |
| Large Animal | Porcine myocardial infarction, canine pacing-induced heart failure | Closer similarity to human physiology and heart size | Higher costs, ethical considerations, limited transgenic models 6 |
| Reagent/Cell Type | Primary Functions | Research Applications |
|---|---|---|
| Neonatal Rat Cardiomyocytes | Hypertrophy assessment, signaling studies, drug screening | Response to hypertrophic stimuli (phenylephrine, angiotensin II), sarcomeric organization analysis 6 |
| Adult Cardiomyocytes | Contractility measurement, calcium transient analysis, pathophysiological studies | Isolation from diseased hearts, assessment of mechanical function, single-cell electrophysiology 6 |
| Human iPSC-derived Cardiomyocytes | Disease modeling, personalized medicine, drug toxicity testing | Studying human genetic disorders, patient-specific therapy optimization, high-throughput safety pharmacology 6 |
| Biomaterials | Providing scaffolds for tissue engineering, improving device compatibility | Cardiac patches, vascular grafts, stents with enhanced blood compatibility 4 |
The presentation particularly emphasized the evolving sophistication of human iPSC-derived cardiomyocytes, which now allow researchers to study human-specific disease mechanisms without relying solely on animal models that may not fully recapitulate human physiology. These cells, derived from adult skin or blood cells reprogrammed to an embryonic-like state, can then be differentiated into beating heart cells that carry a patient's specific genetic background—enabling truly personalized cardiovascular medicine 6 .
| Molecular Component | Normal Heart | Remodeled Heart | Functional Consequence |
|---|---|---|---|
| Myosin Heavy Chain | Predominantly α-isoform | Shift toward β-isoform | Reduced contractility, slower contraction velocity 1 |
| SERCA2a | High expression | Decreased expression | Impaired calcium sequestration, diastolic dysfunction 1 |
| Fetal Genes | Low expression | Reexpressed (ANF, BNP) | Marker of pathological stress, contributes to maladaptation 1 |
| Connexin 43 | Localized to intercalated discs | Redistributed along cell sides | Slowed conduction, increased arrhythmia risk 1 |
| Collagen | Organized network | Excessive, disorganized deposition | Tissue stiffness, diastolic dysfunction, arrhythmogenic substrate 1 |
The translational potential of cardiovascular research took center stage at BCVS 2018, with several emerging technologies poised to transform patient care in the coming decades.
The field of cardiovascular biomaterials has evolved from creating biologically inert structures to designing sophisticated materials that actively interact with biological systems 4 . The global biomaterials market was projected to reach $88.4 billion by 2017, with cardiovascular applications representing the dominant category at approximately $20.7 billion 4 . This investment is driving innovations like:
Provide temporary scaffolding after angioplasty then dissolve, eliminating long-term complications of permanent metal implants 4 .
Promote natural lining of implants by the body's own cells, dramatically improving compatibility and reducing thrombosis risk 4 .
Infused with living cardiomyocytes that can be grafted onto damaged heart areas to restore contractile function 4 .
While not new, medications targeting the renin-angiotensin system continue to be cornerstone therapies for preventing pathological remodeling. ACE inhibitors (ending in "-pril") and ARBs (ending in "-sartan") have demonstrated significant benefits in slowing remodeling progression across multiple clinical conditions 2 5 . Interestingly, these medications provide protection even for patients without high blood pressure, indicating their direct anti-remodeling effects beyond blood pressure control 2 .
Several presentations explored gene therapy approaches for modulating key mediators of cardiac remodeling. Targets included:
Enhancing expression improves both contraction and relaxation in failing hearts
Regulating this natural brake on SERCA2a improves calcium cycling
Targeting mediators of collagen deposition reduces pathological scarring
The 2018 Basic Cardiovascular Sciences Scientific Sessions revealed a field in the midst of a transformative period. The traditional boundaries between biology, engineering, and computational science are blurring, giving rise to integrated approaches that promise to revolutionize how we combat heart disease. From the detailed understanding of molecular switches like STIM1 that control hypertrophy, to the development of intelligent biomaterials that integrate with living tissue, researchers are building an impressive arsenal against our number one killer.
What makes this era particularly exciting is the convergence of multiple disciplines—biology, engineering, informatics, and material science—all focused on decoding and defending the human heart.
The research highlighted at BCVS 2018 underscores a fundamental shift from simply managing symptoms to truly understanding and reversing the underlying pathological processes. While challenges remain in effectively translating these discoveries to clinical practice, the scientific foundation being laid today points toward a future where heart failure may become a more manageable, even reversible condition, rather than an inevitable decline.
As these innovations continue to evolve, the day may come when repairing a damaged heart is as routine as mending a broken bone—a testament to the dedication of the researchers gathering each year at conferences like BCVS to share their latest discoveries in the relentless pursuit of saving lives.