Browsing by Subject "Cardiovascular"

Now showing 1 - 5 of 5

Algal derivative rhamnan sulfate reduces vascular inflammation and atherosclerotic plaque formation
(2022-05) Patil, Nikita P.; Baker, Aaron Blair; Rausch, Manuel; Tanaka, Hirofumi; Ghosh, Debadyuti
The glycocalyx, an interior lining of blood vessels, forms a barrier against atherosclerotic risk factors. It is degraded during plaque development, allowing cholesterol deposition and inflammation in the intima. Rhamnan sulfate (RS), a polysaccharide from green seaweed, resembles heparan sulfate, a component of the glycocalyx which can replace and rejuvenate the glycocalyx to enhance barrier function and prevent plaque formation. In vitro, we tested the interaction of RS with vascular cells and its effects on their proliferation, migration and inhibition of the NF-κb pathway. We also tested the effects of RS on glycocalyx stiffness and thickness post-inflammation. In vivo, we conducted a study in female and male ApoE [superscript -/-] mice on a high fat diet where RS treatment was provided orally. We found that RS decreased growth factor induced proliferation and migration of endothelial and vascular smooth muscle cells. It also decreased the activation of NF-κb in response to TNF-α treatment while binding to NF-κb subunits. Mechanical properties of the glycocalyx could be restored with RS under certain inflammatory conditions. ApoE [superscript -/-] mice, oral consumption of RS decreased cholesterol levels in the plasma in female mice and plaque area in both female and male mice. In livers of these mice, RS treatment showed significant differences in genes related to metabolism, circadian rhythm and lipid regulation between high fat diet and RS groups and male and female mice.
Cerebrovascular dysfunction : associations with midlife risk factors
(2021-05-08) Gourley, Drew David; Tanaka, Hirofumi, Ph. D.; Haley, Andreana P; Kohl, Harold W; Lalande, Sophie
While age has the strongest associations with the development of dementia, a myriad of modifiable cardiovascular risk factors exacerbates and accelerate such risk. Identifying the individual and combined effect earlier in life is crucial to reduce their impact and to introduce positive changes in health behaviors. This dissertation focused on associations between traditional cardiovascular risk factors as well as novel measures of vascular pathology to identify negative functional and structural changes in the brain and cerebrovascular circulation. The rationale for these projects is that continued investigation on the impact of individual and aggregate risk from various cardiovascular risk factors will help target early changes in structure and function that contribute to late life cognitive decline. Once clinical deficits are present, it is often too late to intervene. Therefore, the target population was placed on early to late middle-aged adults between 40-64. In the first study, cross-sectional associations between a midlife dementia risk score composed of cardiovascular risk factors and measures of structural integrity in the brain were investigated. We measured the association between two algorithm-based risk scores used to assess dementia and vascular risk with neuroimaging and cognitive measures in middle-aged, cognitively intact adults. The primary findings of the first study were that the dementia risk score was negatively associated with cortical thickness in the superior frontal gyrus and parahippocampal gyrus as well as memory. These findings provide insight into early pathological changes that occur even among low-risk adults. In the second study, we investigated if subclinical elevations in blood glucose concentration were associated with an early marker of cognitive dysfunction, functional connectivity, and whether this relation was modified by physical fitness or physical activity status. We determined the moderating effect of physical fitness on the association between elevated plasma glucose and functional connectivity. We found there was no direct effect of elevated plasma glucose or insulin resistance with functional connectivity between the medial prefrontal cortex and posterior cingulate cortex, and that neither physical fitness nor physical activity status moderated this association. This suggests that there is a threshold at which elevations in metabolic factors influence connectivity. For the last study, we examined the association between midlife extracranial and peripheral atherosclerosis with late-life intracranial atherosclerosis using a novel magnetic resonance angiography technique. Using the community-based Atherosclerosis Risk in Communities study, we examined the association between various measures of extracranial and peripheral atherosclerosis and late-life intracranial atherosclerosis. We found that carotid intima media thickness was associated with greater odds of intracranial plaque presence and a greater burden of intracranial atherosclerotic disease. Taken together, our findings emphasize the importance of improving lifestyle behaviors at midlife as well as before the emergence of clinical pathology, such as diabetes, to reduce risk of late life dysfunction.
The efficacy of Nexersys training for improving body composition and cardiovascular fitness
(2013-05) Saeugling, Lee Daniel; Coyle, Edward F., 1952-
Purpose: This is the first study done to determine the efficacy of 10-weeks of Nexersys training on improving cardiovascular fitness (CF) and body composition (BC). Nexersys is an "exergaming" system that combines mixed martial arts, high-intensity interval training and core work into an interactive unit with a monitor and 7-strike pads. Participants were provided a Nexersys unit in their homes to complete 10-weeks of training 3 to 4 times a week progressing from 5, 3-min rounds with a minute rest to 15 rounds at the end of 10-weeks. Participants were tested on 3 separate occasions, prior to beginning training (0wk), at 5-weeks (5wk) and 10-weeks (10wk). Body mass (BM), percent body fat (%BF), fat mass (FM) and lean mass (LM) were assessed using dual-energy X-ray absorptiometry (DEXA). CF was assessed during a 10-round Nexersys bout (NB) and a VO2max treadmill (VO2max) test. CF during NB and VO2max treadmill test was assessed by using regression analysis to determine the estimated average heart rate for a range of VO2 10-25 ml/kg/min (HRN) and 10-30 ml/kg/min (HRV) respectively. Results and Conclusion: Relative to starting values, BM did not change (79.8 ± 7.9 to 79.7 ± 7.5 kg). %BF and FM decreased from starting values (36.0 ± 3.4% to 34.1 ± 5.3%, p=0.003 and 30.0 ± 4.9 kg to 28.4 ± 4.6 kg, p=0.045, respectively). LM increased from starting values (46.7 ± 3.5kg to 48.4 ± 3.6kg, p=0.001). HRN and HRV decreased from starting (148 ± 2.7 to 140.8 ± 1.9 bpm, p=0.003 and 148 ± 1.8 to 140.1 ± 1.8 bpm, p=0.003, respectively). VO2max trended to increase but did not reach statistical significance (33.9 ± 1.7 to 36.3 ± 1.7 ml/kg/min, p=0.054). These findings suggest 10-weeks of Nexersys training improves body composition both by increasing LM and decreasing BF with no change in BM. CF improved at submaximal intensities.
On the 3D contractile properties of the aortic heart valve interstitial cell in health and disease
(2022-05-02) Khang, Alex, Ph. D.; Sacks, Michael S.; Anseth, Kristi S; Baker, Aaron B; Cosgriff-Hernandez, Elizabeth M; Ferrari, Giovanni
Aortic valve interstitial cells (AVICs) are fibrobast-like cells that reside within all layers of the aortic valve (AV) and maintain extracellular matrix (ECM) turnover and remodeling. In disease, AVICs can undergo activation and take on a myofibroblastic phenotype characterized by increases in ECM deposition, remodeling, and cellular contractility brought about through expression of alpha-smooth muscle actin stress fibers (SFs). AVIC contractility via stress fibers is a physical indicator that reflects both AVIC activation level as well as biophysical state and is known to be correlated with crucial processes such as collagen deposition and ECM remodeling. My dissertation focuses on investigating the 3D contractile properties of AVICs within tissue-mimicking, 3D peptide-modified poly (ethlyene glycol) (PEG) hydrogels that crucially allow for direct visualization and assessment of AVIC behaviors. First, I used a flexure setup to quantify the contractile states of AVICs embedded within PEG gels, which showed similarity to our earlier native tissue work and demonstrated that the PEG gel environment reproduces many of the same functional characteristics as soft tissue. Then, I investigated the 3D contractile properties of AVICs in greater detail using 3D traction force microscopy and found that AVIC shape orientation and principal contractile direction were correlated. Further analysis showed that AVIC protrusions were the main drivers of AVIC contractile behaviors and that they deformed in a uniform, piston-like manner, indicative of highly-aligned underlying SFs. To gain deeper insight into SF architecture and contractile forces, I developed a 3D computational model of the contracting AVIC within a PEG hydrogel medium. First, the model predicted that AVICs stiffen the local material likely due to nascent ECM deposition. The local variations in hydrogel moduli were then incorporated with a mechanical model of the contracting AVIC which predicted that the greatest SF alignment and contractile force levels were localized at the AVIC protrusions, showing consistency with experimentation. Finally, I extended this approach to investigate intrinsic differences between AVICs extracted from human bicuspid AVs (BAVs) and structurally normal tricuspid AVs (NAVs) and found that AVICs from BAVs showed lower levels of activation as evidenced by lesser SF alignment and contractility. These findings suggest that intrinsic differences among the AVICs likely contribute to the increased rate of valve disease experienced by many BAV patients. In addition, this work highlights the importance of investigating cellular and sub-cellular differences among the BAV and NAV toward identifying targets for novel, non-surgical therapies.
Photoacoustic image guidance and tissue characterization in cardiovascular applications
(2016-12) Dana, Nicholas Pacheco; Suggs, Laura J.; Emelianov, Stanislav Y.; Dunn, Andrew; Tunnell, James; Bouchard, Richard
Collectively, cardiovascular diseases continue to be the leading cause of death, across nations and across decades. Improved diagnostic imaging methods offer promise to alleviate the morbidity associated with these diseases. Photoacoustic (PA) imaging is one such method, poised to make a significant impact on cardiovascular imaging, both as a research tool, as well as a clinical imaging modality. Offering the potential of molecular imaging in real-time, PA methods have been demonstrated in proof-of-concept studies tracking myocyte calcium dynamics. These results open the door to non-invasive longitudinal assessment of cardiac electrophysiological function, with implications for drug and contrast agent development. PA image guidance has also been extended to the characterization of cardiac radiofrequency ablation lesions. This method has been demonstrated to utilize endogenous chromophore changes resulting from ablation for the generation of depth-resolved tissue characterization maps, capable of assessing lesion extent. The technique has been subsequently validated by assessing high-intensity focused ultrasound ablation lesions in myocardium, with the hope for offering thermographic capabilities as well. While PA imaging offers such promise in cardiac ablation procedures, it is also in the process of clinical translation for image guidance and characterization in coronary artery disease applications. Research has shown, using Monte Carlo optical modeling, that using a simple dual-wavelength PA imaging technique has great potential for successful visualization of atherosclerotic plaques across multiple tissue types and at clinically relevant multiple millimeters of depth. Collectively these results offer a suite of PA imaging tools with the potential for molecular and thermographic imaging across a broad range of cardiovascular applications.