Relation of high levels of high-density lipoprotein cholesterol to coronary artery disease and systemic hypertension

Hamad, Abdullah; Salameh, Muwaffaq; Mahmoud, Hatim; Singh, Jaya; Zaghmout, Mohammad; Ward, Laurie

doi:10.1016/s0002-9149(01)01902-6

Cited by 2 publications

(5 citation statements)

References 15 publications

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“…Hypertension impairs cardiac function ( 23 – 26 ) and alters HDL structure and function ( 9 , 22 ). HDL protects against I/R injury in vivo and ex vivo , reviewed in ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, hypertension is a major risk factor of cardiovascular diseases (CVD), whereby increased blood pressure attributes to 47% of coronary heart disease (CHD) cases ( 4 , 5 ). Moreover, blood pressure lowering is an effective strategy in reducing blood pressure related deaths ( 6 – 9 ). Control randomized clinical trials demonstrated that patients at high cardiovascular risk or patients with established CVD benefit from blood pressure lowering treatments whether they were normotensive or hypertensive ( 6 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

“…Reduced HDL-C levels and impaired HDL synthesis and turnover were reported in patients with mild hypertension ( 21 ). Furthermore, increased blood pressure eliminated the protective effects of HDL against CHD and stroke ( 9 ). HDL function and composition were altered by hypertension and anti-hypertensive drugs.…”

Section: Introductionmentioning

confidence: 99%

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High Density Lipoprotein Reduces Blood Pressure and Protects Spontaneously Hypertensive Rats Against Myocardial Ischemia-Reperfusion Injury in an SR-BI Dependent Manner

Al-Jarallah

Babiker

2022

Front. Cardiovasc. Med.

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BackgroundHypertension is a key risk factor in the development of cardiovascular diseases. Elevation in blood pressure alters high density lipoprotein (HDL) function and composition. The exact role of HDL in cardiovascular complications observed in hypertension is however not clearly understood. HDL protected against myocardial ischemia/reperfusion (I/R) injury in normotensive rats. Nonetheless, it's not clear if restoration of HDL function and/or composition protects against myocardial I/R injury in spontaneously hypertensive rats (SHR).ObjectivesIn this study we tested the effect of HDL treatment on I/R injury in Wistar Kyoto rats (WKY) and SHR and investigated the possible underlying mechanism(s).MethodsHDL (900 ng/kg/min) or vehicle were continuously administered to 11-week old WKY and SHR for 1 week (chronic treatment). Blood pressure was measured before and after treatment. Hearts were subjected to I/R injury using a modified Langendorff system. Another set of rats were treated with HDL administered at reperfusion (acute treatment) in the presence or absence of scavenger receptor class B type-I (SR-BI) blocking antibody. Cardiac hemodynamics were computed and cardiac enzyme release and infarct size were measured. Total cholesterol (TC) and HDL-cholesterol (HDL-C) were enzymatically assayed. Markers of autophagy and inflammation were detected by immunoblotting and ELISA, respectively.ResultsHDL treatment did not increase TC or HDL-C levels in SHR or WKY, yet it significantly (P < 0.01) reduced systolic and diastolic blood pressure in SHR. Chronic and acute HDL treatment significantly (P < 0.05) protected WKY and SHR against myocardial I/R injury. Chronic HDL treatment was significantly (P < 0.05) more protective in SHR whereas acute HDL treatment induced significantly (P < 0.05) greater protection in WKY. The extent of HDL induced protection was proportional to the expression levels of cardiac SR-BI and blockage of SR-BI completely abolished HDL mediated protection in SHR. Chronic HDL treatment significantly (P < 0.05) reduced markers of autophagy and inflammation in hypertensive rats.ConclusionsWe demonstrate a novel anti-hypertensive and a cardioprotective effect of HDL against myocardial I/R injury in SHR, the magnitude of which is directly related to the expression levels of cardiac SR-BI. Mechanistically, chronic HDL treatment protected SHR hearts by reducing autophagy and inflammation.

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“…Hypertension impairs cardiac function ( 23 – 26 ) and alters HDL structure and function ( 9 , 22 ). HDL protects against I/R injury in vivo and ex vivo , reviewed in ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High Density Lipoprotein Reduces Blood Pressure and Protects Spontaneously Hypertensive Rats Against Myocardial Ischemia-Reperfusion Injury in an SR-BI Dependent Manner

Al-Jarallah

Babiker

2022

Front. Cardiovasc. Med.

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“…Strategies focusing on blood pressure reduction have demonstrated efficacy in mitigating blood pressure-linked fatalities [ 2 ]. Clinical trials have shown that people at high risk of heart problems or those with existing heart disease benefit from blood pressure-lowering treatments, regardless of whether they have normal or high blood pressure [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…The relationship between HDL and hypertension is, however, less clearly understood. Elevated blood pressure nullifies the protective effects of HDL against CHD and stroke [ 3 ]. Hypertension and anti-hypertensive drugs alter HDL function and composition [ 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

High-Density Lipoprotein Signaling via Sphingosine-1-Phosphate Receptors Safeguards Spontaneously Hypertensive Rats against Myocardial Ischemia/Reperfusion Injury

Al-Jarallah,

Babiker

2024

Pharmaceutics

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Background: High-density lipoprotein (HDL) protects against ischemia/reperfusion (I/R) injury via signaling through scavenger-receptor class B type-I (SR-BI) and sphingosine-1-phosphate receptors (S1PRs). We recently reported that HDL protects the hearts of spontaneously hypertensive rats (SHRs) against I/R injury in an SR-BI-dependent manner. Objective: In this study, we examined the role of S1PRs in HDL-induced protection against myocardial I/R injury in hypertensive rats. Methods: Hearts from Wistar Kyoto rats (WKYs) and SHRs were subjected to I/R injury using a modified Langendorff system. The hearts were treated with or without HDL in the presence or absence of a receptor- or kinase-specific antagonist. Cardiac hemodynamics and infarct size were measured. Target proteins were analyzed by immunoblotting and ELISA, and nitrite levels were measured using Greis reagent. Results: HDL protected the hearts of WKYs and SHRs against I/R injury. HDL, however, was more protective in WKYs. HDL protection in SHRs required lipid uptake via SR-BI and S1PR1 and S1PR3 but not S1PR2. The hearts from SHRs expressed significantly lower levels of S1PR3 than the hearts from WKYs. HDL differentially activated mediators of the SAFE and RISK pathways in WKYs and SHRs and resulted in nitric oxide generation. Blockage of these pathways abrogated HDL effects. Conclusions: HDL protects against myocardial I/R injury in normotensive and hypertensive rats, albeit to varying degrees. HDL protection in hearts from hypertensive rodents involved SR-BI-mediated lipid uptake coupled with signaling through S1PR1 and S1PR3. The extent of HDL-induced cardiac protection is directly proportional to S1PR3 expression levels. Mechanistically, the safeguarding effects of HDL involved activation of the SAFE and RISK pathways and the generation of nitric oxide.

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Relation of high levels of high-density lipoprotein cholesterol to coronary artery disease and systemic hypertension

Cited by 2 publications

References 15 publications

High Density Lipoprotein Reduces Blood Pressure and Protects Spontaneously Hypertensive Rats Against Myocardial Ischemia-Reperfusion Injury in an SR-BI Dependent Manner

High Density Lipoprotein Reduces Blood Pressure and Protects Spontaneously Hypertensive Rats Against Myocardial Ischemia-Reperfusion Injury in an SR-BI Dependent Manner

High-Density Lipoprotein Signaling via Sphingosine-1-Phosphate Receptors Safeguards Spontaneously Hypertensive Rats against Myocardial Ischemia/Reperfusion Injury

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