Key result
Surgical MI in mice causes pronounced LV dysfunction and irreversible cardiosplenic and cardiorenal network dysregulation.
This preclinical study demonstrates that myocardial infarction triggers irreversible ventricular dysfunction and dynamic, progressive histological changes in the cardiosplenic and cardiorenal networks, highlighting the need for systems biology approaches in heart failure.
MI-induced cardiosplenic and cardiorenal dysregulation in mice supports systems-level HF research; leaves open human relevance and therapeutic targeting.
Heart failure (HF) secondary to myocardial infarction (MI) is linked to kidney complications that comprise cellular, structural, functional, and survival indicators. However, HF research is focused on left ventricular (LV) pathology. Here, we determined comprehensive functional analysis of the LV using echocardiography in transition from acute heart failure (AHF) to progressive chronic heart failure (CHF) pathology and developed a histological compendium of the cardiosplenic and cardiorenal networks in pathological remodeling. In surgically induced MI using permanent coronary ligation, the LV dysfunction is pronounced, with myocardium necrosis, wall thinning, and 20-30% LV rupture events that indicated AHF and CHF pathological remodeling in C57BL/6 male mice (2-4 mo old, n = 50). Temporal LV function analysis indicated that fractional shortening and strain are reduced from day 1 to day 5 in AHF and sustained to advance to CHF from day 28 to day 56 compared with naïve control mice ( n = 6). During the transition of AHF ( day 1 to day 5) to advanced CHF ( day 28 to day 56), histological and cellular changes in the spleen were definite, with bimodal inflammatory responses in kidney inflammatory biomarkers. Likewise, there was a unidirectional, progressive, and irreversible deposition of compact collagen in the LV along with dynamic changes in the cardiosplenic and cardiorenal networks post-MI. The renal histology and injury markers suggested that cardiac injury triggers irreversible dysregulation that actively alters the cardiosplenic and cardiorenal networks. In summary, the novel strategies or pathways that modulate comprehensive cardiosplenic and cardiorenal networks in AHF and CHF would be effective approaches to study either cardiac repair or cardiac pathology. NEW & NOTEWORTHY The present compendium shows irreversible ventricular dysfunction as assessed by temporal echocardiography while histological and structural measurements of the spleen and kidney added a novel direction to study cardiosplenic and cardiorenal networks in heart failure pathology. Therefore, the consideration of systems biology and integrative approach is essential to develop novel treatments.
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Halade et al. (2017) studied Heart failure secondary to myocardial infarction (n=56). Surgically induced MI using permanent coronary ligation vs. Naïve control mice was evaluated on LV dysfunction and histological changes in cardiosplenic and cardiorenal networks. Surgically induced myocardial infarction in mice caused pronounced LV dysfunction and irreversible dysregulation of cardiosplenic and cardiorenal networks from acute to chronic heart failure.
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