Women in Cardiovascular Therapeutics

Editorial

10 May 2023

Editorial: Women in cardiovascular therapeutics

Liya Yin

Ting Zhou

Ze Zheng

Xiaochun Long

, 1 more and

Hong S. Lu

1,439 views

0 citations

Editors

HONG S LU

University of Kentucky

Liya Yin

Northeast Ohio Medical University

Xiaochun Long

Augusta University

Hongyu Qiu

Georgia State University

Ze Zheng

Medical College of Wisconsin

Ting Zhou

University of Wisconsin-Madison

Impact

Assessment of SMAD3 VUS pathogenicity using a zebrafish embryonic assay. (A) Diagram of the spatial distribution of specific VUS mutations examined. (B) Confocal images of the tail aorta/vein labeled in Tg[kdrl:mCherry] in 48hpf embryos. White dashed boxes indicate the enlargement regions used to highlight differences in diameter (white dashed lines). Embryos imaged were either control, injected with smad3aWT mRNA or smad3aP124T, smad3aR287W, smad3aL296P or smad3aA349P. (C) Quantification of diameter counts. Each point represents an individual embryo measured. Standard deviation is depicted in red. Variants were compared to WT: *p < 0.05, **p < 0.01. (D) Summary of VUS classification changes based on the zebrafish embryonic assay results. P, pathogenic, LP, likely pathogenic.

Brief Research Report

28 February 2023

Novel SMAD3 variant identified in a patient with familial aortopathy modeled using a zebrafish embryo assay

Mary B. Sheppard

, 2 more and

Jakub K. Famulski

2,057 views

4 citations

Effects of empagliflozin treatment on the cardiac microvasculature of db/db mice. (A) Representative transverse images of myocardial vasculature showing capillaries (IB4+, red). (B) Statistical analysis of the density of capillaries in the transverse sections of myocardial tissue between the db/m group, db/db group, and db/db + EMPA group. (C) Representative longitudinal images of myocardial vasculature showing capillaries (IB4+, red). (D) Statistical analysis of the diameter of capillaries in the longitudinal sections of myocardial tissue between the db/m group, db/db group, and db/db + EMPA group. Data are presented as the means ± SEM. P-values are corrected for multiple comparisons. IB4, isolectin B4; HPF, high power field.

Original Research

16 December 2022

Empagliflozin inhibits coronary microvascular dysfunction and reduces cardiac pericyte loss in db/db mice

Yimin Tu

, 11 more and

Yanxiang Gao

4,687 views

8 citations

TSP-1 deletion increases LMOD-1 and calponin expression in aortic vessels of male MetS KKAy+/– mice. Shown are representative western blots for TSP-1, LMOD-1 and calponin expression in aortic lysates derived from (A) male KKAy+/–TSP-1+/+ and KKAy+/–TSP-1–/– mice and (B) female KKAy+/–TSP-1+/+ and KKAy+/–TSP-1–/– mice. Shown are summary graphs for densitometric quantification of immunoblots for (C) TSP-1, (D) Calponin, and (E) LMOD-1 expression. n = 5–7 animals per genotype per sex. All results are expressed as mean ± SEM. *p < 0.05, ***p < 0.0005. Loading control = Ponceau S. Data shown illustrates protein expression normalized to Ponceau S. For representative immunoblots, lane images depict proteins loaded and detected on a single immunoblot (full blots shown in Supplementary Figures 3, 4); however, lanes were re-arranged to improve the clarity of presentation.

Original Research

23 November 2022

Sex-specific differences in atherosclerosis, thrombospondin-1, and smooth muscle cell differentiation in metabolic syndrome versus non-metabolic syndrome mice

Shreya Gupta

, 6 more and

Priya Raman

2,846 views

3 citations

The process of patient attrition in the ability to deliver advanced heart failure therapies. Not all patients with end stage heart failure will undergo advanced heart failure therapies. We must understand the processes of diagnosis, medical management, referral for surgery, and surgical decision making to better address disparities in care. This is challenging as attrition of would-be surgical candidates occurs throughout the healthcare system and across medical and surgical specialties. Future research efforts should focus on medical and socioeconomic aspects of this attrition including but certainly not limited to physician bias, system factors, and patient preferences and limitations.

Mini Review

18 October 2022

Sex-based considerations for implementation of ventricular assist device therapy

K. Candis Jones-Ungerleider

, 5 more and

Paul C. Tang

1,919 views

1 citations

Efferocytosis is the phagocytic process required for maintaining normal vascular hemostasis. Efficient efferocytosis plays an important role in protecting against atherosclerosis by inducing phagocytic signals or “eat-me” signals and clearing apoptotic debris. Conversely, in defective efferocytosis, the phagocytic signals are reduced and the phagocytic ability of apoptotic cells is decreased. As a result, apoptotic cells are converted to necrotic cells, and accumulation of these uncleared cells form a necrotic core, which leads to the release of proatherogenic factors and progression of atherosclerosis plaque. ECs, Endothelial cells; VSMCs, Vascular Smooth Muscle Cells.

Mini Review

30 September 2022

Defective efferocytosis of vascular cells in heart disease

Bandana Singh

, 6 more and

Hong Chen

5,995 views

11 citations

(A–C) Role of endothelial cell CXCR4 on cardiomyocyte hypertrophy. (A) Confocal image of representative immunofluorescent staining with WGA and DAPI to label myocyte membranes. (B) The average area of one cardiomyocyte was determined using WGA and DAPI staining (n = 10–12). (C) Heart weight/body weight ratio (n = 11–17). Our results showed a significantly increased cross-sectional area in cardiomyocytes and HW/BW ratio from EC CXCR4 KO mice compared to control mice. *Indicates a p-value ≤ 0.05 vs. control group.

Original Research

06 September 2022

Role of endothelial CXCR4 in the development of aortic valve stenosis

Anna Winnicki

, 12 more and

Feng Dong

2,666 views

2 citations

Original Research

04 August 2022

Lipocalin-2 in neutrophils induces ferroptosis in septic cardiac dysfunction via increasing labile iron pool of cardiomyocytes

Yuxue Huang

, 6 more and

Jian’an Wang

Cardiac dysfunction is a common complication of sepsis with high mortality. The present study was designed to identify the effect of neutrophil-derived lipocalin-2 (LCN2) in septic cardiac dysfunction (SCD) and its potential mechanism. Wild-type (WT) and LCN2-knockout (LCN2 KO) mice were peritoneally injected with lipopolysaccharide (LPS) to induce SCD. The cardiac function was assessed 12 h after LPS injection by echocardiography. Cardiac tissue was harvested for the evaluation of malonaldehyde (MDA) and prostaglandin E synthase 2 (PTGS2) mRNA levels. LPS induced ferroptosis and SCD in mice. LCN2 deficiency attenuated cardiac injury post-LPS administration. In vitro, LCN2 expression in neutrophils increased in response to LPS. Ferroptosis of cardiomyocytes induced by conditioned medium (CM) from LPS-induced neutrophils of WT mice could be attenuated in CM from LPS-induced neutrophils of LCN2 KO mice. Exogenous LCN2 induced H9C2 cell ferroptosis via increasing labile iron pool (LIP). In conclusion, our results showed that LCN2 deficiency prevented heart dysfunction and ferroptosis in SCD mice and suggested that neutrophil-derived LCN2 might be a promising therapeutic target for SCD.

11,145 views

25 citations